Water → [(1R)-1-cyclopropylethyl] N-[4-(3-cyano-1-cyclopropyl-6-pyrimidin-2-yloxy-indol-2-yl)phenyl]carbamate

HRID 1009664Notes

Reaction equation

[CH:1]1([C@H:4]([O:6][C:7](=[O:30])[NH:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[N:16]([CH:27]4[CH2:29][CH2:28]4)[C:17]4[C:22]([C:23]=3[C:24]#[N:25])=[CH:21][CH:20]=[C:19]([OH:26])[CH:18]=4)=[CH:11][CH:10]=2)[CH3:5])[CH2:3][CH2:2]1.C([O-])([O-])=O.[Cs+].[Cs+].Cl[C:38]1[N:43]=[CH:42][CH:41]=[CH:40][N:39]=1.O>CN(C=O)C>[CH:1]1([C@H:4]([O:6][C:7](=[O:30])[NH:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[N:16]([CH:27]4[CH2:28][CH2:29]4)[C:17]4[C:22]([C:23]=3[C:24]#[N:25])=[CH:21][CH:20]=[C:19]([O:26][C:38]3[N:43]=[CH:42][CH:41]=[CH:40][N:39]=3)[CH:18]=4)=[CH:11][CH:10]=2)[CH3:5])[CH2:3][CH2:2]1

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of (R)-[4-(3-cyano-1-cyclopropyl-6-hydroxy-1H-indol-2-yl)-phenyl]-carbamic acid 1-cyclopropyl-ethyl ester (0.060 g, 0.15 mmol), Cs2CO3 (0.122 g, 0.375 mmol), 2-chloropyrimidine (0.034 g, 0.3 mmol) in DMF (1.5 mL) was stirred at 70° C. for 2 h. After cooling to room temperature the mixture was poured into water (15 mL) and the precipitate was collected via filtration, washed with water, and purified on silica gel (CH2Cl2/EtOAc, 9.5:0.5) to provide (R)-{4-[3-cyano-1-cyclopropyl-6-(pyrimidin-2-yloxy)-1H-indol-2-yl]-phenyl}carbamic acid 1-cyclopropyl-ethyl ester as a solid (72 mg, 100%).

Workup

temperatureAfter cooling to room temperature the mixture
filtrationthe precipitate was collected via filtration
washwashed with water
custompurified on silica gel (CH2Cl2/EtOAc, 9.5:0.5)

Sources & evidence

ORD record: ord-93d470103f974ac69e242bee41337a5b
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07973069B2

Reaction notes

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