Diisopropylethylamine → N-[2-methoxy-4-(8-methyl-2,8-diazaspiro[3.4]octan-2-yl)-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine

HRID 1842815Notes

Reaction equation

HRID 1842815 reaction equation
Cl.Cl.[CH3:3][N:4]1[CH2:11][CH2:10][CH2:9][C:5]21[CH2:8][NH:7][CH2:6]2.F[C:13]1[C:18]([N+:19]([O-:21])=[O:20])=[CH:17][C:16]([NH:22][C:23]2[N:28]=[C:27]([C:29]3[CH:30]=[N:31][N:32]4[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=34)[CH:26]=[CH:25][N:24]=2)=[C:15]([O:38][CH3:39])[CH:14]=1.CCN(C(C)C)C(C)C>CC(N(C)C)=O>[CH3:39][O:38][C:15]1[CH:14]=[C:13]([N:7]2[CH2:8][C:5]3([N:4]([CH3:3])[CH2:11][CH2:10][CH2:9]3)[CH2:6]2)[C:18]([N+:19]([O-:21])=[O:20])=[CH:17][C:16]=1[NH:22][C:23]1[N:28]=[C:27]([C:29]2[CH:30]=[N:31][N:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=23)[CH:26]=[CH:25][N:24]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 71240784N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine2×HCID 717431205-Methyl-2,5-diazaspiro[3.4]octane dihydrochloride2×

Product 1

HCID 71240856N-[2-methoxy-4-(8-methyl-2,8-diazaspiro[3.4]octan-2-yl)-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amineYield 83.3%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

8-Methyl-2,8-diazaspiro[3.4]octane (Intermediate 47, 133 mg, 0.88 mmol) was added to a suspension of N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(pyrazolo[1,5-a]pyridin-3-yl)-pyrimidin-2-amine (Intermediate 155, 280 mg, 0.74 mmol) and DIPEA (0.153 mL, 0.88 mmol) in DMA (3 mL) and the mixture was heated at 100° C. for 1 h. The mixture was then part-purified by ion exchange chromatography, using an SCX column, eluting with 7M methanolic ammonia. Clean fractions were combined and concentrated in vacuo. Further purification by FCC, eluting with 1-8% CH3OH in CH2Cl2 gave the title compound (300 mg) as an orange dry film; 1H NMR: 1.71 (2H, dt), 2.05 (2H, dd), 2.40 (3H, s), 2.67 (2H, t), 3.75 (2H, d), 3.95 (3H, s), 4.11 (2H, d), 6.31 (1H, s), 7.09 (1H, td), 7.28 (1H, d), 7.35-7.41 (1H, m), 8.25 (1H, s), 8.36 (1H, d), 8.47 (1H, s), 8.50 (1H, d), 8.79 (1H, s), 8.79-8.82 (1H, m); m/z: ES+ MH+ 487.30.

Workup

  1. customThe mixture was then part-purified by ion exchange chromatography
  2. washeluting with 7M methanolic ammonia
  3. concentrationconcentrated in vacuo
  4. customFurther purification by FCC
  5. washeluting with 1-8% CH3OH in CH2Cl2

Sources & evidence

ORD record
ord-1ff047a3e7a044ecb2d46bddb6706e3e
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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