Tetrahydrofuran → 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]benzoic acid

HRID 1264628Notes

Reaction equation

HRID 1264628 reaction equation
C[O:2][C:3](=[O:44])[C:4]1[CH:9]=[CH:8][C:7]([C:10](=[O:43])[C:11]([C:41]#[N:42])=[C:12]([NH:24][C@H:25]2[CH2:31][CH2:30][CH2:29][CH2:28][N:27]([CH2:32][C:33](=[O:39])[N:34]3[CH2:38][CH2:37][CH2:36][CH2:35]3)[C:26]2=[O:40])[NH:13][C:14]2[CH:15]=[CH:16][C:17]3[O:21][C:20]([CH3:22])=[CH:19][C:18]=3[CH:23]=2)=[CH:6][CH:5]=1.C1COCC1>O>[C:41]([C:11](=[C:12]([NH:24][C@H:25]1[CH2:31][CH2:30][CH2:29][CH2:28][N:27]([CH2:32][C:33](=[O:39])[N:34]2[CH2:35][CH2:36][CH2:37][CH2:38]2)[C:26]1=[O:40])[NH:13][C:14]1[CH:15]=[CH:16][C:17]2[O:21][C:20]([CH3:22])=[CH:19][C:18]=2[CH:23]=1)[C:10]([C:7]1[CH:8]=[CH:9][C:4]([C:3]([OH:44])=[O:2])=[CH:5][CH:6]=1)=[O:43])#[N:42]

Participants

4

Reactant 2

HCID 8028TetrahydrofuranHCID 700328734-[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 methyl ester

Product 1

HCID 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 acidYield 83.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

The compound of Example 1 (0.442g, 0.740 mmol) was dissolved in 10 mL of 1:1 water:THF and the mixture was cooled to 0° C. To the solution was added LiOH monohydrate (0.31 g, 7.4 mmol). The reaction mixture was allowed to come to room temperature. After stirring for 24 h, the reaction mixture was concentrated by in vacuo and the residue was dissolved in methylene chloride. The mixture was extracted 2×25 mL with water. The combined aqueous layers were neutralized with 1 N HCl to pH 4 and were extracted 2×25 mL with ethyl acetate. The combined ethyl acetate layers were dried over sodium sulfate and concentrated to give the title compound (360 mg, 83%) as yellow solid: MS (ESI, pos. ion) m/z 584 (M+H); HPLC (method B) tR=3.8 min, purity: >96%.

Workup

  1. customto come to room temperature
  2. concentrationthe reaction mixture was concentrated by in vacuo
  3. dissolutionthe residue was dissolved in methylene chloride
  4. extractionThe mixture was extracted 2×25 mL with water
  5. extractionwere extracted 2×25 mL with ethyl acetate
  6. dry with materialThe combined ethyl acetate layers were dried over sodium sulfate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-2e86c2a03dc3463cb6dabee706c20811
Source dataset
uspto-grants-2003_04
Patent number
US06544981B2

Reaction notes

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