Diisopropylethylamine → Methyl 4-(1-(2-(2-benzylpyrrolidin-1-yl)-5-chloronicotinamido)cyclopropyl)benzoate

HRID 72488Notes

Reaction equation

HRID 72488 reaction equation
[CH2:1]([CH:8]1[CH2:12][CH2:11][CH2:10][N:9]1[C:13]1[N:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:14]=1[C:15]([OH:17])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[NH2:24][C:25]1([C:28]2[CH:37]=[CH:36][C:31]([C:32]([O:34][CH3:35])=[O:33])=[CH:30][CH:29]=2)[CH2:27][CH2:26]1.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>CN(C)C=O>[CH2:1]([CH:8]1[CH2:12][CH2:11][CH2:10][N:9]1[C:13]1[N:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:14]=1[C:15]([NH:24][C:25]1([C:28]2[CH:37]=[CH:36][C:31]([C:32]([O:34][CH3:35])=[O:33])=[CH:30][CH:29]=2)[CH2:27][CH2:26]1)=[O:17])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 66824369Methyl 4-(1-aminocyclopropyl)benzoate hydrochlorideHCID 679582562-(2-Benzylpyrrolidin-1-yl)-5-chloronicotinic acid

Product 1

HCID 67958026Methyl 4-(1-(2-(2-benzylpyrrolidin-1-yl)-5-chloronicotinamido)cyclopropyl)benzoateYield 61.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-(2-benzylpyrrolidin-1-yl)-5-chloronicotinic acid (D100) (70 mg, 0.22 mmol), methyl 4-(1-aminocyclopropyl)benzoate (D7) (50.31 mg, 0.22 mmol) and N,N-Diisopropylethylamine (0.115 ml, 0.66 mmol) in dimethylformamide (5 ml) was stirred at room temperature for 1 h. (Benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (PyBOP) (137.9 mg, 0.265 mmol) was added and the resulting mixture was stirred overnight at room temperature. The reaction mixture was poured into ice-water and extracted with diethyl ether (3×15 ml). The combined organic layers were washed with brine (2×10 ml), dried over Na2SO4, filtered and concentrated. The crude residue was purified by Biotage column (10 g) eluting with a mixture dichloromethane/ethylacetate from 100/0 to 90/10. Collected fractions, after solvent evaporation, afforded the title compound (D144) (66 mg)

Workup

  1. additionwas added
  2. extractionextracted with diethyl ether (3×15 ml)
  3. washThe combined organic layers were washed with brine (2×10 ml)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was purified by Biotage column (10 g)
  8. washeluting with a mixture dichloromethane/ethylacetate from 100/0 to 90/10
  9. customCollected fractions, after solvent evaporation

Sources & evidence

ORD record
ord-187b77fa204848f2b0db51fc0340e26a
Source dataset
uspto-grants-2014_09
Patent number
US08828987B2

Reaction notes

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