Diisopropylethylamine → N-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine

HRID 1842809Notes

Reaction equation

HRID 1842809 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[CH:28]=[N:29][N:30]4[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=34)[CH:24]=[CH:23][N:22]=2)=[C:13]([O:36][CH3:37])[CH:12]=1.CCN(C(C)C)C(C)C>CC(N(C)C)=O>[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[CH:28]=[N:29][N:30]5[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=45)[CH:24]=[CH:23][N:22]=3)=[C:13]([O:36][CH3:37])[CH:12]=2)[CH2:6]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 22121220N,N-dimethylazetidin-3-amine dihydrochloride2×HCID 71240784N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine2×

Product 1

HCID 71240790N-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amineYield 72%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
85 °C

Procedure

N,N-Dimethylazetidin-3-amine dihydrochloride (Intermediate 26, 227 mg, 1.31 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, 415 mg, 1.09 mmol) and DIPEA (0.755 mL, 4.36 mmol) in DMA (3.2 mL) and the mixture was heated at 85° C. for 1 h. The mixture was part-purified 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 0-7% CH3OH in CH2Cl2 gave the title compound (360 mg, 72%) as an orange solid; 1H NMR: 2.15 (6H, s), 3.12-3.19 (1H, m), 3.74-3.78 (2H, m), 3.95 (3H, s), 4.04-4.09 (2H, m), 6.29 (1H, s), 7.08 (1H, td), 7.28 (1H, d), 7.36-7.41 (1H, m), 8.26 (1H, s), 8.35 (1H, d), 8.45-8.49 (2H, m), 8.78 (1H, s), 8.80 (1H, d); m/z: ES+ MH+ 461.33.

Workup

  1. customThe mixture was part-purified by ion exchange chromatography
  2. washeluting with 7M methanolic ammonia
  3. concentrationconcentrated in vacuo
  4. customFurther purification by FCC
  5. washeluting with 0-7% CH3OH in CH2Cl2

Sources & evidence

ORD record
ord-d416abb6bb974273abcc69391515a34a
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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