1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Methyl 4-(4-(4-aminophenyl)-1-methyl-1H-pyrrole-2-carboxamido)-1-methyl-1H-pyrrole-2-carboxylate

Two eq of EDCI and 2.5 eq of DMAP were added to a stirred solution of 6 (0.45 gm, 1.2 eq) in DMF (8 mL) and the mixture was allowed to stir for 30 minutes after which commercially available methyl 4-amino-1-methyl-1H-pyrrole-2-carboxylate (0.18 g, 1.18 mmol, 1.0 eq) was added. The reaction mixture was allowed to stir for a further 6 hour at which point TLC showed completion of reaction. The reaction was quenched by pouring it onto a mixture of ice/water mixture and the resulting mixture was extracted with ethyl acetate (3×150 mL). The combined extracts were sequentially washed with citric acid (100 mL), saturated aqueous NaHCO3 (100 mL), water (100 mL), brine (100 mL) and finally dried over MgSO4. Excess ethyl acetate was evaporated by rotary evaporator under reduced pressure and the crude product 9a (0.58 gm, yield 90.6%) was used for the boc deprotection step to afford 9 without further purification. For boc deprotection, 0.29 gm of 9a was dissolved in a small volume of MeOH and 4M HCl in dioxane (15 mL) was added slowly to the stirring solution. The reaction mixture was stirred for 6 hours at which point TLC showed completion of reaction. Excess solvent was evaporated under vacuum to obtain a brown coloured solid (9). The solid product was subjected to flash chromatography (n-hexane/EtOAc 9:1) to give pure 9. Yield 0.21 gm, 95%.

1. additionwas added
2. customcompletion of reaction
3. customThe reaction was quenched
4. additionby pouring it
5. additiononto a mixture of ice/water mixture
6. extractionthe resulting mixture was extracted with ethyl acetate (3×150 mL)
7. washThe combined extracts were sequentially washed with citric acid (100 mL), saturated aqueous NaHCO3 (100 mL), water (100 mL), brine (100 mL)
8. dry with materialfinally dried over MgSO4
9. customExcess ethyl acetate was evaporated by rotary evaporator under reduced pressure
10. customto afford 9
11. customwithout further purification
12. dissolutionFor boc deprotection, 0.29 gm of 9a was dissolved in a small volume of MeOH and 4M HCl in dioxane (15 mL)
13. additionwas added slowly to the stirring solution
14. stirringThe reaction mixture was stirred for 6 hours at which point TLC
15. customcompletion of reaction
16. customExcess solvent was evaporated under vacuum

ORD record

ord-78dbb84e2d4641cb9cc814c2bc624012

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09321774B2