Reoprt on analysis of raw materials for purification

data

1. Weekly Report CRD 18-Sep-2023 -30-Sep-2023

2. Synthesis of bilastine impurities

3. Bil OXO IMP-D S.N Date Input Reagents Output % Yield Remarks 1 7-9-2023 20 g (BIL-DEO) TEE (1.05 Eq ), NaH (1.5 Eq ) DMF (3.0V) 16 g 68% HPLC 99.2% Sample Send for NMR and MASS analysis Target qty 5.0 g

4. S.N Date Input Reagents Output % Yield Remarks 1 7-9-2023 3.5g (BIL-MEOXO) Dil HCl (3.0 V), NaOH (5V) 3.5 g No data carried out 2 12-9-2023 20 g (BIL-MEOXO) Dil HCl (3.0 V), NaOH (5V) 19 g Crude HPLC show 50 % of IMPURITY F 4 18-9-2023 19g Crude Column Purification Obtain 1.5 g AyUSH Target qty 2.0 g Bilastine IMP-F

5. S.N Date Input Reagents Output % Yield Remarks 1 14-9-2023 3.0g (BIL-OXO) Dil HCl (3.0 V), DCM 5 h 60°C 2.5 g crude 82 % HPLC 88% (need to take back up and purification ) 2 18-9-2023 5.0g (BIL-OXO) Dil HCl (3.0 V), DCM 5 h 60°C 4.5 g crude 82 % 3 20-9-2023 4.5 g Column purification 2.5 g Under analysis Target qty 2.0 g Bilastine IMP-C

6. S.N Date Input Reagents Output % Yield Remarks 1 20-9-2023 10g PPD KSM1 CDI (1.5 Eq ), Aq Amonia DMF 70 °C No Product formed 2 22-9-2023 5.0 PPD Ester Amonia GasTHF 100 °C Starting recovered 3 25-9-2023 2.5g PPD KSM1 SOCl2 (1.5 Eq ), Amonia GasTHF 70 °C 1.0 g 40% On going 4 25-9-2023 5.0 PPD Ester Recovered Amonia GasTHF 110 °C 2.5 g 50 % Submitted TO analytical Dept Target qty 2.0 g Prucalopride IMP-B

7. S.N Date Input Reagents Output % Yield Remarks 1 20-9-2023 10g PPD KSM1 SOCl 2 , MeOH 6H Reflux 9.0 g 84% Submitted for 1HNMR analysis 2 22-9-2023 20g PPD KSM1 SOCl 2 , MeOH 6H Reflux 18.0 g 84% Backup for synthesis of amide from ester Ayush Target qty 2.0 g Prucalopride IMP-D

8. S.N Date Input Reagents Output % Yield Remarks 1 21-9-2023 10 g TCP TFA (3.0V), DCM 0°C to RT 5 H 10 g Crude Use as crude Prucalopride IMP

9. S.N Date Input Reagents Output % Yield Remarks 1 21-9-2023 2g PPD KSM1 DeBOC TCP (1.2Eq),CDI (1.5 Eq ), TEA , DMF 70 °C 1.0 crude No product formed Target qty 1.0 g Prucalopride IMP

10. S.N Date Input Reagents Output % Yield Remarks 1 21-9-2023 1.0g PPD KSM1 HCl , 12H Reflux On going 1 21-9-2023 1.0g PPD KSM1 Aq NaOH,12H Reflux On going Ayush Planed reaction as per requirement od analytical to identify the unknown impurity Prucalopride IMP

11. S.N Date Input Reagents Output % Yield Remarks 1 7-9-2023 5g SM 1 Br2(3.0 V), DCM 2.5 g crude No data carried out 2 18-9-2023 10 g SM 1 Br2(3.0 V), DCM 8.0 g crude No data carried out 2 28-9-2023 25g SM 1 Br2(3.0 V), DCM 30 G crude No data carried out Ayush Target qty 2.0 g Phenylephrine Hydrochloride IMP

12. S.N Date Input Reagents Output % Yield Remarks 1 9-9-2023 2.5g SM 1 Methyl amine, THF 2.5 g crude No data carried out 2 19-9-2023 8.5 g SM 1 Methyl amine, THF 5.0 g Under analysis as per availability of HPLC Ayush Target qty 2.0 g Phenylephrine Hydrochloride IMP

13. S.N Date Input Reagents Output % Yield Remarks 1 5-9-2023 4g D- Prolanimide CAC (1.05 Eq ),POCl 3 (1.05 Eq ) DCM:DMF (3.0V) 3.5 g 56% NMR & Mass Consistent Completed Vildagliptin IMP

14. S.N Date Input Reagents Output % Yield Remarks 1 26-9-2023 5.0 g VGP KOH (5.0 eq ) Ethanol 5.0 Crude Peak Shop is not good 1 28-9-2023 5.0 g VGP NaOH (5.0 eq ) Methanol 5.0 G crude No response on HHPLC Vildagliptin IMP

15. Completed Interpretation Documentation (19-9-2023) and 29-9-2023 PPD-KSM 1 CDCA BIL-IMP D (BIL-OXO ) PPD IMP D PPD IMP B BIL IMP F BILIMP E