Ammonium Chloride → 4-(3-Dimethylaminoazetidin-1-yl)-6-methoxy-N-[4-(1-methylindol-3-yl)pyrimidin-2-yl]benzene-1,3-diamine

HRID 1842770Notes

Reaction equation

HRID 1842770 reaction equation
[CH3:1][N:2]([CH3:35])[CH:3]1[CH2:6][N:5]([C:7]2[C:12]([N+:13]([O-])=O)=[CH:11][C:10]([NH:16][C:17]3[N:22]=[C:21]([C:23]4[C:31]5[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=5)[N:25]([CH3:32])[CH:24]=4)[CH:20]=[CH:19][N:18]=3)=[C:9]([O:33][CH3:34])[CH:8]=2)[CH2:4]1.[NH4+].[Cl-]>C(O)C.O.[Fe]>[CH3:35][N:2]([CH3:1])[CH:3]1[CH2:4][N:5]([C:7]2[CH:8]=[C:9]([O:33][CH3:34])[C:10]([NH:16][C:17]3[N:22]=[C:21]([C:23]4[C:31]5[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=5)[N:25]([CH3:32])[CH:24]=4)[CH:20]=[CH:19][N:18]=3)=[CH:11][C:12]=2[NH2:13])[CH2:6]1

Participants

6

Reactant 2

HCID 25517Ammonium ChlorideHCID 71240795N-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-4-(1-methylindol-3-yl)pyrimidin-2-amine2×

Product 1

HCID 866773434-(3-Dimethylaminoazetidin-1-yl)-6-methoxy-N-[4-(1-methylindol-3-yl)pyrimidin-2-yl]benzene-1,3-diamineYield 80%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A mixture of N-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-4-(1-methylindol-3-yl)pyrimidin-2-amine (Intermediate 117, 160 mg, 0.34 mmol), iron (113 mg, 2.03 mmol) and NH4Cl (13.56 mg, 0.25 mmol) in ethanol (5 mL) and water (1.67 mL) was heated at reflux for 2 h. The cooled mixture was purified by ion exchange chromatography, using an SCX column and eluting with 1:1 7M methanolic ammonia in CH2Cl2. Appropriate fractions were combined and concentrated in vacuo. Further purification by FCC, eluting with 0-5% 7N methanolic ammonia in CH2Cl2 gave the title compound (120 mg, 80%) as a brown gum; m/z: ES+ MH+ 444.61.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 h
  3. customThe cooled mixture was purified by ion exchange chromatography
  4. washeluting with 1:1 7M methanolic ammonia in CH2Cl2
  5. concentrationconcentrated in vacuo
  6. customFurther purification by FCC
  7. washeluting with 0-5% 7N methanolic ammonia in CH2Cl2

Sources & evidence

ORD record
ord-98b50e8df47844d1b721550de7c55c8f
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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