1,1'-Carbonyldiimidazole → (+/-)-5-(6-(benzyloxymethyl)pyrimidin-4-yloxy)-N-(4-methoxy-3-(trifluoromethyl)phenyl)-1H-indole-1-carboxamide

HRID 450262Notes

Reaction equation

HRID 450262 reaction equation
[CH2:1]([O:8][CH2:9][C:10]1[N:15]=[CH:14][N:13]=[C:12]([O:16][C:17]2[CH:18]=[C:19]3[C:23](=[CH:24][CH:25]=2)[NH:22][CH:21]=[CH:20]3)[CH:11]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1N=CN([C:31]([N:33]2C=N[CH:35]=[CH:34]2)=[O:32])C=1.[CH3:38][O:39][C:40]1[CH:46]=CC(N)=[CH:42][C:41]=1[C:47]([F:50])([F:49])[F:48]>ClCCCl.C(Cl)Cl>[CH2:1]([O:8][CH2:9][C:10]1[N:15]=[CH:14][N:13]=[C:12]([O:16][C:17]2[CH:18]=[C:19]3[C:23](=[CH:24][CH:25]=2)[N:22]([C:31]([NH:33][C:34]2[CH:35]=[CH:46][C:40]([O:39][CH3:38])=[C:41]([C:47]([F:50])([F:49])[F:48])[CH:42]=2)=[O:32])[CH:21]=[CH:20]3)[CH:11]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 6007055-Amino-2-methoxybenzotrifluorideHCID 593942601H-Indole, 5-[[6-[(phenylmethoxy)methyl]-4-pyrimidinyl]oxy]-

Product 1

HCID 59394510(+/-)-5-(6-(benzyloxymethyl)pyrimidin-4-yloxy)-N-(4-methoxy-3-(trifluoromethyl)phenyl)-1H-indole-1-carboxamide

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-(6-(benzyloxymethyl)pyrimidin-4-yloxy)-1H-indole (0.8 g, 2.41 mmol) in 35 mL of DCE, CDI (1.17 g, 7.24 mmol) is added followed by TEA (1 mL, 7.24 mmol). Mixture is stirred at rt overnight and then 4-methoxy-3-(trifluoromethyl)aniline (1.38 g, 7.24 mmol) is added followed by stirring for 4 days. The reaction is diluted with DCM, washed with saturated aqueous NaHCO3 (×2), brine, and the organic layer is dried over Na2SO4. After concentration, the residue is purified by FCC (5-60% EtOAc/heptane) to give the title compound. MS (ESI) m/z 549.1 (M+1).

Workup

  1. stirringby stirring for 4 days
  2. washwashed with saturated aqueous NaHCO3 (×2), brine
  3. dry with materialthe organic layer is dried over Na2SO4
  4. concentrationAfter concentration
  5. customthe residue is purified by FCC (5-60% EtOAc/heptane)

Sources & evidence

ORD record
ord-bf852b307fc24d6b9de6f90158e80c0a
Source dataset
uspto-grants-2013_07
Patent number
US08486954B2

Reaction notes

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