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 643825Notes

Reaction equation

HRID 643825 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7]([O:19][C@H:20]3[CH2:24][NH:23][C@H:22]([C:25]([NH:27][C@:28]4([C:33]([OH:35])=[O:34])[CH2:30][C@H:29]4[CH:31]=[CH2:32])=[O:26])[CH2:21]3)=[CH:8][C:9]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[N:10]2)=[CH:5][CH:4]=1.[C:36](=[O:39])([O-])O.[Na+].C(Cl)(Cl)=O.[C:45]([O:49][C:50]([NH:52][NH:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH:59]=[CH2:60])=[O:51])([CH3:48])([CH3:47])[CH3:46].O1CC[CH2:63][CH2:62]1>>[CH2:62]([O:34][C:33]([C:28]1([NH:27][C:25]([CH:22]2[CH2:21][CH:20]([O:19][C:7]3[C:6]4[C:11](=[CH:12][C:3]([O:2][CH3:1])=[CH:4][CH:5]=4)[N:10]=[C:9]([C:13]4[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=4)[CH:8]=3)[CH2:24][N:23]2[C:36]([N:53]([CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH:59]=[CH2:60])[NH:52][C:50]([O:49][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:51])=[O:39])=[O:26])[CH2:30][CH:29]1[CH:31]=[CH2:32])=[O:35])[CH3:63]

Participants

6

Reactant 5

HCID 6371PhosgeneHCID 8028TetrahydrofuranHCID 516892Sodium Bicarbonate2×HCID 58719488tert-Butyl 2-(hept-6-en-1-yl)hydrazine-1-carboxylateHCID 68493021HCID 68493021, compound

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%

Procedure

Compound 15 (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%→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%→2% methanol in ether)

Sources & evidence

ORD record
ord-4d1f989fe368412b9d4c0c664a930e43
Source dataset
uspto-grants-2010_04
Patent number
US07700552B2

Reaction notes

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