Phosgene → 1-{[1-[1-(2-Hydroxy-indan-1-ylcarbamoyl)-2,2-dimethyl-propylcarbamoyl]-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester

HRID 1822433Notes

Reaction equation

HRID 1822433 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-:41])(O)=O.[Na+].C(Cl)(Cl)=O.[NH2:47][CH:48]([C:62]([CH3:65])([CH3:64])[CH3:63])[C:49]([NH:51][CH:52]1[C:60]2[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=2)[CH2:54][CH:53]1[OH:61])=[O:50]>C1COCC1.C1(C)C=CC=CC=1>[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](=[O:41])[NH:47][CH:48]([C:49](=[O:50])[NH:51][CH:52]2[C:60]3[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=3)[CH2:54][CH:53]2[OH:61])[C:62]([CH3:65])([CH3:63])[CH3:64])=[O:13])[CH2:8][CH:7]1[CH:9]=[CH2:10])=[O:5])[CH3:2]

Participants

7

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 68488353HCID 68488353, compound

Product 1

HCID 684916281-{[1-[1-(2-Hydroxy-indan-1-ylcarbamoyl)-2,2-dimethyl-propylcarbamoyl]-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of compound 12 (0.13 mmol) in THF (2 mL), was added a large excess of NaHCO3 (s) and a solution of phosgene in toluene (1.6 M, 600 μL). After 10 min of agitation the slurry was filtered and concentrated to dryness. The solid was redissolved in dichloromethane and a large excess of NaHCO3 (s) and 2-Amino-N-(2-hydroxy-indan-1-yl)-3,3-dimethyl-butyramide (0.65 mmol) was added. The slurry was agitated for 24-40 hrs at RT. The slurry was filtered, concentrated and subjected to silica column chromatography (gradient elution from 100% DCM to MeOH/DCM 2:98) to give the title compound (89.6 mg, 0.11 mmol). Purity by HPLC>95%. M+H+790.3.

Workup

  1. filtrationAfter 10 min of agitation the slurry was filtered
  2. concentrationconcentrated to dryness
  3. dissolutionThe solid was redissolved in dichloromethane
  4. filtrationThe slurry was filtered
  5. concentrationconcentrated
  6. washsubjected to silica column chromatography (gradient elution from 100% DCM to MeOH/DCM 2:98)

Sources & evidence

ORD record
ord-d21af08ca24347b9adb361426472cc9e
Source dataset
uspto-grants-2009_10
Patent number
US07608590B2

Reaction notes

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