Ammonium Chloride → N'-[4-(1H-indol-3-yl)pyrimidin-2-yl]-4-methoxy-6-(4-methylpiperazin-1-yl)benzene-1,3-diamine

HRID 1842724Notes

Reaction equation

[NH4+].[Cl-].[NH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([NH:18][C:19]3[CH:24]=[C:23]([N+:25]([O-])=O)[C:22]([N:28]4[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]4)=[CH:21][C:20]=3[O:35][CH3:36])[N:13]=2)=[CH:4]1>O.C(O)C.[Fe]>[NH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([NH:18][C:19]3[CH:24]=[C:23]([NH2:25])[C:22]([N:28]4[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]4)=[CH:21][C:20]=3[O:35][CH3:36])[N:13]=2)=[CH:4]1

Participants

Conditions

Temperature: 105 °C

Procedure

A solution of NH4Cl (0.021 g, 0.38 mmol) in water (3 mL) was added in one portion to a stirred suspension of 4-(1H-indol-3-yl)-N-[2-methoxy-4-(4-methylpiperazin-1-yl)-5-nitrophenyl]pyrimidin-2-amine (Intermediate 67, 0.235 g, 0.51 mmol) and iron (0.171 g, 3.07 mmol) in ethanol (9 mL) and the mixture was stirred at 105° C. for 18 h. The mixture was then concentrated in vacuo and the resulting residue was dissolved in DMF (20 mL). Purification by ion exchange chromatography, using an SCX column, eluting with 0.35M methanolic ammonia in CH2Cl2 and concentration of the appropriate fractions gave the title compound (0.206 g, 94%) as a yellow solid; m/z: ES+ MH+ 430.51.

Workup

concentrationThe mixture was then concentrated in vacuo
dissolutionthe resulting residue was dissolved in DMF (20 mL)
customPurification by ion exchange chromatography
washeluting with 0.35M methanolic ammonia in CH2Cl2 and concentration of the appropriate fractions

Sources & evidence

ORD record: ord-488bea28bb164e798bdab266afe93115
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08946235B2

Reaction notes

Loading…