Isopropyl chloroformate → Propan-2-yl (2-chloro-4-{3-cyano-1-cyclobutyl-6-[(pyrimidin-2-yl)oxy]-1H-indol-2-yl}phenyl)carbamate

HRID 506141Notes

Reaction equation

HRID 506141 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH:26]3[CH2:29][CH2:28][CH2:27]3)[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][C:3]=1[Cl:30].Cl[C:32]([O:34][CH:35]([CH3:37])[CH3:36])=[O:33]>C(Cl)Cl.N1C=CC=CC=1.C1(C)C=CC=CC=1.Cl>[CH:35]([O:34][C:32](=[O:33])[NH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH:26]3[CH2:29][CH2:28][CH2:27]3)[C:10]3[C:15]([C:16]=2[C:17]#[N:18])=[CH:14][CH:13]=[C:12]([O:19][C:20]2[N:21]=[CH:22][CH:23]=[CH:24][N:25]=2)[CH:11]=3)=[CH:4][C:3]=1[Cl:30])([CH3:37])[CH3:36]

Participants

7

Reactant 2

HCID 7917Isopropyl chloroformateHCID 594306702-(4-amino-3-chloro-phenyl)-1-cyclobutyl-6-(pyrimidin-2-yloxy)-1H-indole-3-carbonitrile

Product 1

HCID 25050998Propan-2-yl (2-chloro-4-{3-cyano-1-cyclobutyl-6-[(pyrimidin-2-yl)oxy]-1H-indol-2-yl}phenyl)carbamateYield 93%

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 1049PyridineSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

To 2-(4-amino-3-chloro-phenyl)-1-cyclobutyl-6-(pyrimidin-2-yloxy)-1H-indole-3-carbonitrile (0.26 g, 0.6 mmol) in CH2Cl2 (0.5 mL) and pyridine (0.5 mL) was added a solution of isopropyl chloroformate in toluene (1.0M, 0.8 mL) and the mixture was stirred at room temperature overnight. The mixture was diluted with aq. HCl (1N) and extracted with CH2Cl2. The organic layer was washed with water and brine, dried, concentrated and purified on silica gel (40% EtOAc/hexane) to provide {2-chloro-4-[3-cyano-1-cyclobutyl-6-(pyrimidin-2-yloxy)-1H-indol-2-yl]-phenyl}-carbamic acid isopropyl ester (0.29 g, 93%) as a white solid.

Workup

  1. extractionextracted with CH2Cl2
  2. washThe organic layer was washed with water and brine
  3. customdried
  4. concentrationconcentrated
  5. custompurified on silica gel (40% EtOAc/hexane)

Sources & evidence

ORD record
ord-08010a6180854d0fbcc90c6c799830cb
Source dataset
uspto-grants-2010_08
Patent number
US07781478B2

Reaction notes

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