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

HRID 502298Notes

Reaction equation

[NH2:1][C:2]1N=[CH:6][C:5]([C:8]2[N:9]([CH:26]3[CH2:29][CH2:28]C3)[C:10]3[C:15]([C:16]=2[C:17]#[N:18])=[CH:14][CH:13]=[C:12]([O:19][C:20]2[N:25]=[CH:24][CH:23]=[CH:22][N:21]=2)[CH:11]=3)=[CH:4][CH:3]=1.C1C([N+]([O-])=O)=CC=C([Cl-][C:40]([O-])=[O:41])C=1.[CH:43]1([C@H:46]([OH:48])[CH3:47])[CH2:45][CH2:44]1.N1C=CC=C[CH:50]=1>O.C(Cl)Cl>[CH:43]1([C@H:46]([O:48][C:40](=[O:41])[NH:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]3[N:9]([CH:26]4[CH2:29][CH2:28]4)[C:10]4[C:15]([C:16]=3[C:17]#[N:18])=[CH:14][CH:13]=[C:12]([O:19][C:20]3[N:21]=[CH:22][CH:23]=[CH:24][N:25]=3)[CH:11]=4)=[CH:6][CH:50]=2)[CH3:47])[CH2:45][CH2:44]1

Participants

Conditions

Temperature: 30 °C

Procedure

A mixture of 2-(6-amino-pyridin-3-yl)-1-cyclobutyl-6-(pyrimidin-2-yloxy)-1H-indole-3-carbonitrile (115 mg, 0.3 mmol), 4-nitrophenylchloroformate (91 mg, 0.45 mmol) in pyridine (1.0 mL) was stirred at 30° C. for 2 h, followed by the addition of (R)-1-cyclopropylethanol (150 μL, 1.5 mmol). The mixture was stirred at 80° C. overnight and diluted with water (10 mL) and CH2Cl2 (5 mL). The organic layer was washed with water (3×5 mL), HCl (2N, 3×5 mL), sat. aq. NaHCO3 (3×5 mL) and and purified on silica gel (CH2Cl2/EtOAc, 1:9) to provide (R)-{4-[3-cyano-1-cyclopropyl-6-(pyrimidin-2-yloxy)-1H-indol-2-yl]-phenyl}-carbamic acid 1-cyclopropylethyl ester (25 mg, 17%).

Workup

stirringThe mixture was stirred at 80° C. overnight
washThe organic layer was washed with water (3×5 mL), HCl (2N, 3×5 mL), sat. aq. NaHCO3 (3×5 mL)
custompurified on silica gel (CH2Cl2/EtOAc, 1:9)

Sources & evidence

ORD record: ord-448c2c567cac41faa6afb564b97a55d8
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07772271B2

Reaction notes

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