1,2-Ethanediamine, N1,N1,N2-trimethyl- → N'-(2-dimethylaminoethyl)-2-methoxy-N'-methyl-5-nitro-N-(4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)benzene-1,4-diamine

HRID 1842811Notes

Reaction equation

[CH3:1][N:2]([CH3:7])[CH2:3][CH2:4][NH:5][CH3:6].F[C:9]1[C:14]([N+:15]([O-:17])=[O:16])=[CH:13][C:12]([NH:18][C:19]2[N:24]=[C:23]([C:25]3[CH:26]=[N:27][N:28]4[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=34)[CH:22]=[CH:21][N:20]=2)=[C:11]([O:34][CH3:35])[CH:10]=1.CCN(C(C)C)C(C)C>CC(N(C)C)=O>[CH3:1][N:2]([CH3:7])[CH2:3][CH2:4][N:5]([CH3:6])[C:9]1[C:14]([N+:15]([O-:17])=[O:16])=[CH:13][C:12]([NH:18][C:19]2[N:24]=[C:23]([C:25]3[CH:26]=[N:27][N:28]4[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=34)[CH:22]=[CH:21][N:20]=2)=[C:11]([O:34][CH3:35])[CH:10]=1

Participants

Conditions

Temperature: 85 °C

Procedure

N1,N1,N2-trimethylethane-1,2-diamine (138 mg, 1.35 mmol) was added to a suspension of N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine (Intermediate 155, 428 mg, 1.13 mmol) and DIPEA (0.234 mL, 1.35 mmol) in DMA (3.3 mL), and the mixture was heated at 85° C. for 1.5 h. Part-purification was achieved by ion exchange chromatography, using an SCX column and eluting with 7M methanolic ammonia. Clean fractions were combined and concentrated in vacuo. Further purification by FCC, eluting with 0-10% CH3OH in CH2Cl2 gave the title compound (444 mg, 85%) as an orange oil; 1H NMR: 2.18 (6H, s), 2.50-2.53 (2H, m), 2.87 (3H, s), 3.26-3.30 (2H, m), 3.95 (3H, s), 6.86 (1H, s), 7.09 (1H, td), 7.30 (1H, d), 7.35-7.40 (1H, m), 8.27 (1H, s), 8.37 (1H, d), 8.47-8.51 (2H, m), 8.79 (1H, s), 8.79-8.82 (1H, m); m/z: ES+ MH+ 463.33.

Workup

customPart-purification
washeluting with 7M methanolic ammonia
concentrationconcentrated in vacuo
customFurther purification by FCC
washeluting with 0-10% CH3OH in CH2Cl2

Sources & evidence

ORD record: ord-87550bfcd7744a45b6cfdee9372c3270
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08946235B2

Reaction notes

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