Indoline → Tert-butyl 3-[4-(2-{4-[(2,3-dihydro-indole-1-carbonyl)-amino]-3-methoxy-phenyl}-acetylamino)-phenyl]-butyrate

HRID 1167808Notes

Reaction equation

HRID 1167808 reaction equation
ClC(Cl)(O[C:5](=[O:11])OC(Cl)(Cl)Cl)Cl.[NH2:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][C:21]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([CH:30]([CH3:39])[CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])=[CH:26][CH:25]=2)=[O:22])=[CH:16][C:15]=1[O:40][CH3:41].[NH:42]1[C:50]2[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=2)[CH2:44][CH2:43]1>ClCCl.C(N(CC)CC)C>[N:42]1([C:5]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([CH2:20][C:21]([NH:23][C:24]3[CH:29]=[CH:28][C:27]([CH:30]([CH3:39])[CH2:31][C:32]([O:34][C:35]([CH3:36])([CH3:37])[CH3:38])=[O:33])=[CH:26][CH:25]=3)=[O:22])=[CH:16][C:15]=2[O:40][CH3:41])=[O:11])[C:50]2[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=2)[CH2:44][CH2:43]1

Participants

6

Reactant 3

HCID 10328IndolineHCID 94429TriphosgeneHCID 22994176Tert-butyl 3-[4-({4-amino-3-methoxyphenyl}acetylamino)phenyl]butyrate

Product 1

HCID 22994266Tert-butyl 3-[4-(2-{4-[(2,3-dihydro-indole-1-carbonyl)-amino]-3-methoxy-phenyl}-acetylamino)-phenyl]-butyrate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

Triphosgene (150 mg) was added to a stirred solution of tert-butyl 3-[4-({4-amino-3-methoxyphenyl}acetylamino)phenyl]butyrate (540 mg, Reference Example 2) in dichloromethane (50 ml) at 0-5° C. under an atmosphere of nitrogen. After stirring for one hour the mixture was treated with a solution of indoline (0.15 ml) in dichloromethane (2.5 ml) and triethylamine (0.51 ml). This mixture was allowed to stand at room temperature overnight and then evaporated. The residual gummy solid was suspended in water and the suspension was acidified to pH 1 by addition of hydrochloric acid. The resulting pale green solid was filtered and then subjected to flash chromatography on silica eluting with 0.2% to 1% methanol in dichloromethane to give the title compound (580 mg) as an off-white solid.

Workup

  1. waitto stand at room temperature overnight
  2. customevaporated
  3. additionthe suspension was acidified to pH 1 by addition of hydrochloric acid
  4. filtrationThe resulting pale green solid was filtered

Sources & evidence

ORD record
ord-4b586571773d4d0d8afe78a917fb1476
Source dataset
uspto-grants-2003_09
Patent number
US06620832B2

Reaction notes

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