2-Chloroethyl isocyanate → N-(3,4-Difluorobenzyl)-6-(4,5-dihydrooxazol-2-ylamino)-2-isopropyl-1-(pyridin-2-ylmethyl)-1H-indole-3-carboxamide

HRID 40152Notes

Reaction equation

HRID 40152 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:21]([NH:23][CH2:24][C:25]3[CH:30]=[CH:29][C:28]([F:31])=[C:27]([F:32])[CH:26]=3)=[O:22])=[C:7]([CH:18]([CH3:20])[CH3:19])[N:8]2[CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)=[CH:4][CH:3]=1.Cl[CH2:34][CH2:35][N:36]=[C:37]=[O:38]>C(Cl)Cl>[F:32][C:27]1[CH:26]=[C:25]([CH:30]=[CH:29][C:28]=1[F:31])[CH2:24][NH:23][C:21]([C:6]1[C:5]2[C:9](=[CH:10][C:2]([NH:1][C:37]3[O:38][CH2:34][CH2:35][N:36]=3)=[CH:3][CH:4]=2)[N:8]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)[C:7]=1[CH:18]([CH3:20])[CH3:19])=[O:22]

Participants

4

Reactant 2

HCID 160352-Chloroethyl isocyanateHCID 59762386HCID 59762386, compound2×

Product 1

HCID 59762444N-(3,4-Difluorobenzyl)-6-(4,5-dihydrooxazol-2-ylamino)-2-isopropyl-1-(pyridin-2-ylmethyl)-1H-indole-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 6-amino-N-(3,4-difluorobenzyl)-2-isopropyl-1-(pyridin-2-ylmethyl)-1H-indole-3-carboxamide (Compound 182, 48 mg, 0.11 mmol) in CH2Cl2 (1 ml) was added chloroethyl isocyanate (10 μl, 0.12 mmol). The reaction was stirred at room temperature for 16 h, and the solvent was removed. To the residue was added H2O and the mixture was heated at 80° C. for 3 h, diluted with EtOAc, washed with aqueous K2CO3 and brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by chromatography on silica gel (0→100% EtOAc-hexanes) to yield the title compound.

Workup

  1. customthe solvent was removed
  2. additionTo the residue was added H2O
  3. temperaturethe mixture was heated at 80° C. for 3 h
  4. additiondiluted with EtOAc
  5. washwashed with aqueous K2CO3 and brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by chromatography on silica gel (0→100% EtOAc-hexanes)

Sources & evidence

ORD record
ord-5154365e3b5a477eb8e92ec0ec4fafcb
Source dataset
uspto-grants-2013_09
Patent number
US08524917B2

Reaction notes

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