Dimethylamine → 4-[2-Cyano-3-[[(3s)-hexahydro-2-oxo-1-[2-oxo-2-(1-pyrrolidinyl)ethyl]-1h-azepin-3-yl]amino]-3-[(2-methyl-5-benzofuranyl)amino]-1-oxo-2-propenyl]-n,n-dimethylbenzamide

HRID 1264629Notes

Reaction equation

HRID 1264629 reaction equation
[C:1]([C:3](=[C:15]([NH:27][C@H:28]1[CH2:34][CH2:33][CH2:32][CH2:31][N:30]([CH2:35][C:36](=[O:42])[N:37]2[CH2:41][CH2:40][CH2:39][CH2:38]2)[C:29]1=[O:43])[NH:16][C:17]1[CH:18]=[CH:19][C:20]2[O:24][C:23]([CH3:25])=[CH:22][C:21]=2[CH:26]=1)[C:4]([C:6]1[CH:14]=[CH:13][C:9]([C:10](O)=[O:11])=[CH:8][CH:7]=1)=[O:5])#[N:2].[CH3:44][N:45](C(F)=[N+](C)C)[CH3:46].F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.CNC.C1COCC1>C(#N)C.CO>[C:1]([C:3](=[C:15]([NH:27][C@H:28]1[CH2:34][CH2:33][CH2:32][CH2:31][N:30]([CH2:35][C:36](=[O:42])[N:37]2[CH2:41][CH2:40][CH2:39][CH2:38]2)[C:29]1=[O:43])[NH:16][C:17]1[CH:18]=[CH:19][C:20]2[O:24][C:23]([CH3:25])=[CH:22][C:21]=2[CH:26]=1)[C:4]([C:6]1[CH:14]=[CH:13][C:9]([C:10]([N:45]([CH3:46])[CH3:44])=[O:11])=[CH:8][CH:7]=1)=[O:5])#[N:2]

Participants

8

Reactant 5

HCID 674DimethylamineHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 2774761Tetramethylfluoroformamidinium hexafluorophosphateHCID 700323634-[2-Cyano-3-[[(3s)-hexahydro-2-oxo-1-[2-oxo-2-(1-pyrrolidinyl)ethyl]-1h-azepin-3-yl]amino]-3-[(2-methyl-5-benzofuranyl)amino]-1-oxo-2-propenyl]benzoic acid

Product 1

HCID 700302894-[2-Cyano-3-[[(3s)-hexahydro-2-oxo-1-[2-oxo-2-(1-pyrrolidinyl)ethyl]-1h-azepin-3-yl]amino]-3-[(2-methyl-5-benzofuranyl)amino]-1-oxo-2-propenyl]-n,n-dimethylbenzamideYield 72%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent2×

Procedure

The compound of Example 2 (59 mg, 0.10 mmol) was dissolved in 1 mL of acetonitrile. To the solution was added TFFH (26.4 mg, 0.10 mmol) and triethylamine (0.016 mL, 0.11 mmol). The reaction mixture was stirred at room temperature for 30 min and then 2 M dimethyl amine in THF (0.060 mL, 0.12 mmol) was added. The reaction mixture was stirred at room temperature for an additional 2 h. The reaction mixture was loaded onto a SCX cartridge (prewashed with methanol and then acetonitrile). The column was eluted with acetonitrile, 1/1 acetonitrile/methanol and methanol to provide the title compound (44 mg, 72%) as a white solid: MS (ESI, pos. ion spectrum) m/z 611 (M+H); HPLC (method B) tR 3.7 min, purity 100%.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for an additional 2 h
  2. washThe column was eluted with acetonitrile, 1/1 acetonitrile/methanol and methanol

Sources & evidence

ORD record
ord-acf0781927b34168b7de6822fca51776
Source dataset
uspto-grants-2003_04
Patent number
US06544981B2

Reaction notes

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