Diisopropylethylamine → Methyl 4-(1-(5-chloro-2-(2-phenylpyrrolidin-1-yl)nicotinamido)cyclopropyl)benzoate

HRID 72486

Reaction equation

HRID 72486 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:11]2[CH2:15][CH2:14][CH2:13][CH:12]2[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:6]([CH:10]=1)[C:7](O)=[O:8].Cl.[NH2:23][C:24]1([C:27]2[CH:36]=[CH:35][C:30]([C:31]([O:33][CH3:34])=[O:32])=[CH:29][CH:28]=2)[CH2:26][CH2:25]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>[Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:11]2[CH2:15][CH2:14][CH2:13][CH:12]2[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:6]([CH:10]=1)[C:7]([NH:23][C:24]1([C:27]2[CH:36]=[CH:35][C:30]([C:31]([O:33][CH3:34])=[O:32])=[CH:29][CH:28]=2)[CH2:26][CH2:25]1)=[O:8]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 66824369Methyl 4-(1-aminocyclopropyl)benzoate hydrochlorideHCID 679586975-Chloro-2-(2-phenylpyrrolidin-1-yl)nicotinic acid

Product 1

HCID 67958454Methyl 4-(1-(5-chloro-2-(2-phenylpyrrolidin-1-yl)nicotinamido)cyclopropyl)benzoateYield 79.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 5-chloro-2-(2-phenylpyrrolidin-1-yl)nicotinic acid (D98) (150 mg, 0.5 mmol), methyl 4-(1-aminocyclopropyl)benzoate hydrochloride (D7) (114 mg, 0.5 mmol) and N,N-Diisopropylethylamine (194 mg, 1.5 mmol) in dimethylformamide (10 ml) was stirred 1 h at room temperature, then benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP) (312 mg, 0.6 mmol) was added. The mixture was stirred at room temperature overnight, then poured into ice-water (20 ml) and extracted with ethyl acetate (2×20 ml). The organic solution was washed with brine (40 ml), dried over Na2SO4 and concentrated to obtain a residue which was purified by flash chromatography on silica gel eluting with a mixture petroleum ether/ethyl acetate (4:1). Collected fractions after solvent evaporation afforded the title compound (D142) (189 mg) as a yellow solid.

Workup

  1. extractionextracted with ethyl acetate (2×20 ml)
  2. washThe organic solution was washed with brine (40 ml)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customto obtain a residue which
  6. customwas purified by flash chromatography on silica gel eluting with a mixture petroleum ether/ethyl acetate (4:1)
  7. customCollected fractions after solvent evaporation

Sources & evidence

ORD record
ord-e84c069f9dc145f299776fd8598a3879
Source dataset
uspto-grants-2014_09
Patent number
US08828987B2

Linked notes

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