Phosgene → 1-{[1-(N'-tert-Butoxycarbonyl-N-hept-6-enyl-hydrazinocarbonyl)-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester

HRID 1822471Notes

Reaction equation

HRID 1822471 reaction equation
[CH2:1]([O:3][C:4]([C:6]1([NH:11][C:12]([CH:14]2[CH2:18][CH:17]([O:19][C:20]3[C:29]4[C:24](=[CH:25][C:26]([O:30][CH3:31])=[CH:27][CH:28]=4)[N:23]=[C:22]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[CH:21]=3)[CH2:16][NH:15]2)=[O:13])[CH2:8][CH:7]1[CH:9]=[CH2:10])=[O:5])[CH3:2].[C:38](=O)([O-])[OH:39].[Na+].C(Cl)(Cl)=O.[C:47]([O:51][C:52]([NH:54][NH:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH:61]=[CH2:62])=[O:53])([CH3:50])([CH3:49])[CH3:48]>O1CCCC1>[CH2:1]([O:3][C:4]([C:6]1([NH:11][C:12]([CH:14]2[CH2:18][CH:17]([O:19][C:20]3[C:29]4[C:24](=[CH:25][C:26]([O:30][CH3:31])=[CH:27][CH:28]=4)[N:23]=[C:22]([C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=4)[CH:21]=3)[CH2:16][N:15]2[C:38]([N:55]([CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH:61]=[CH2:62])[NH:54][C:52]([O:51][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:53])=[O:39])=[O:13])[CH2:8][CH:7]1[CH:9]=[CH2:10])=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 6371PhosgeneHCID 516892Sodium Bicarbonate2×HCID 207653161-{[4-(7-Methoxy-2-phenyl-quinolin-4-yloxy)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl esterHCID 58719488tert-Butyl 2-(hept-6-en-1-yl)hydrazine-1-carboxylate

Product 1

HCID 685786161-{[1-(N'-tert-Butoxycarbonyl-N-hept-6-enyl-hydrazinocarbonyl)-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl esterYield 79%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Compound 12 (200 mg, 0.4 mmol) was dissolved in tetrahydrofuran (10 ml). A tea-spoon of sodium hydrogencarbonate was added, followed by phosgene (1.8 μl, 1.9 M in toluene). The reaction mixture was stirred for 30 min and filtrated. The solvent was evaporated and the crude chloride was re-dissolved in dichloromethane (10 ml). Sodium hydrogencarbonate (1 tea-spoon) and N′-hept-6-enyl-hydrazinecarboxylic acid tert.butyl ester (182 mg, 0.8 mmol). The reaction mixture was stirred at room temp. for 40 h. and then filtrated and purified by silica chromatography (1% methanol in ether →2% methanol in ether) to give pure title product (240 mg, 79%).

Workup

  1. filtrationfiltrated
  2. customThe solvent was evaporated
  3. dissolutionthe crude chloride was re-dissolved in dichloromethane (10 ml)
  4. stirringThe reaction mixture was stirred at room temp. for 40 h.
  5. filtrationfiltrated
  6. custompurified by silica chromatography (1% methanol in ether →2% methanol in ether)

Sources & evidence

ORD record
ord-885d3d458f1e4cc7a430b1d322fba703
Source dataset
uspto-grants-2009_10
Patent number
US07608590B2

Reaction notes

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