Diisopropylethylamine → N-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-4-(1-methylindol-3-yl)pyrimidin-2-amine

HRID 1842771Notes

Reaction equation

HRID 1842771 reaction equation
Cl.Cl.[CH3:3][N:4]([CH3:9])[CH:5]1[CH2:8][NH:7][CH2:6]1.F[C:11]1[C:16]([N+:17]([O-:19])=[O:18])=[CH:15][C:14]([NH:20][C:21]2[N:26]=[C:25]([C:27]3[C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[N:29]([CH3:36])[CH:28]=3)[CH:24]=[CH:23][N:22]=2)=[C:13]([O:37][CH3:38])[CH:12]=1.ClC1C(C2C3C(=CC=CC=3)N(C)C=2)=NC(NC2C=C([N+]([O-])=O)C(F)=CC=2OC)=NC=1.CCN(C(C)C)C(C)C>FC(F)(F)CO.CO>[CH3:3][N:4]([CH3:9])[CH:5]1[CH2:8][N:7]([C:11]2[C:16]([N+:17]([O-:19])=[O:18])=[CH:15][C:14]([NH:20][C:21]3[N:26]=[C:25]([C:27]4[C:35]5[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=5)[N:29]([CH3:36])[CH:28]=4)[CH:24]=[CH:23][N:22]=3)=[C:13]([O:37][CH3:38])[CH:12]=2)[CH2:6]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 22121220N,N-dimethylazetidin-3-amine dihydrochloride2×HCID 71239058N-(4-Fluoro-2-methoxy-5-nitrophenyl)-4-(1-methyl-1H-indol-3-yl)pyrimidin-2-amineHCID 712392825-chloro-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1-methylindol-3-yl)pyrimidin-2-amine

Product 1

HCID 71240795N-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-4-(1-methylindol-3-yl)pyrimidin-2-amineYield 89%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 64092,2,2-TrifluoroethanolSolvent

Conditions

Temperature
140 °C

Procedure

N,N-dimethylazetidin-3-amine dihydrochloride (Intermediate 26, 79 mg, 0.46 mmol) was added to a suspension of N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1-methylindol-3-yl)pyrimidin-2-amine (Intermediate 129 (which may be prepared by the method described for Intermediate 87), 150 mg, 0.38 mmol) and DIPEA (0.264 mL, 1.53 mmol) in 2,2,2-trifluoroethanol (3 mL). The mixture was heated at 140° C. in a microwave for 1 h. The mixture was then purified directly by ion exchange chromatography, using an SCX column (50 g) and eluting with 1:1 7M methanolic ammonia in CH2Cl2. Concentration of appropriate fractions in vacuo gave a brick red solid. This solid was suspended in CH3OH and the solid was collected by filtration, washed with CH3OH (10 mL) and dried in vacuo to give the title compound (160 mg, 89%) as a red solid; m/z: ES+ MH+ 474.61.

Workup

  1. custommay be prepared by the method
  2. customThe mixture was then purified directly by ion exchange chromatography
  3. washeluting with 1:1 7M methanolic ammonia in CH2Cl2
  4. customConcentration of appropriate fractions in vacuo gave a brick red solid
  5. filtrationthe solid was collected by filtration
  6. washwashed with CH3OH (10 mL)
  7. customdried in vacuo

Sources & evidence

ORD record
ord-36946ef56e9047eeb4b7e05dfa0ed839
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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