Acryloyl chloride → N-{5-[(5-Chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)amino]-4-methoxy-2-[5-methyl-2,5-diazaspiro[3.4]octan-2-yl]phenyl}prop-2-enamide

HRID 1842619Notes

Reaction equation

HRID 1842619 reaction equation
[C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[Cl:6][C:7]1[C:8]([C:32]2[CH:33]=[N:34][N:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=23)=[N:9][C:10]([NH:13][C:14]2[CH:15]=[C:16]([NH2:31])[C:17]([N:22]3[CH2:25][C:24]4([CH2:29][CH2:28][CH2:27][N:26]4[CH3:30])[CH2:23]3)=[CH:18][C:19]=2[O:20][CH3:21])=[N:11][CH:12]=1>C(Cl)Cl>[Cl:6][C:7]1[C:8]([C:32]2[CH:33]=[N:34][N:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=23)=[N:9][C:10]([NH:13][C:14]2[C:19]([O:20][CH3:21])=[CH:18][C:17]([N:22]3[CH2:23][C:24]4([CH2:29][CH2:28][CH2:27][N:26]4[CH3:30])[CH2:25]3)=[C:16]([NH:31][C:1](=[O:4])[CH:2]=[CH2:3])[CH:15]=2)=[N:11][CH:12]=1

Participants

4

Reactant 2

HCID 13140Acryloyl chlorideHCID 86677239N'-(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-4-methoxy-6-(5-methyl-2,5-diazaspiro[3.4]octan-2-yl)benzene-1,3-diamine2×

Product 1

HCID 86677238N-{5-[(5-Chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)amino]-4-methoxy-2-[5-methyl-2,5-diazaspiro[3.4]octan-2-yl]phenyl}prop-2-enamideYield 64.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of acryloyl chloride (5.71 mg, 0.06 mmol) in CH2Cl2 (1 mL) was added dropwise to a mixture of N′-(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-4-methoxy-6-(5-methyl-2,5-diazaspiro[3.4]octan-2-yl)benzene-1,3-diamine (Intermediate 45, 31 mg, 0.06 mmol) in CH2Cl2 (5 mL), which was cooled in an ice/water bath. The mixture was stirred for 3 h and then washed with brine, dried (Na2SO4) and concentrated in vacuo. Purification by FCC, eluting with 0-2% 7N methanolic ammonia in CH2Cl2 gave the title compound (21 mg, 61%) as a yellow foam; 1H NMR: 1.70 (2H, dd), 1.98-2.11 (2H, m), 2.37 (3H, s), 2.62 (2H, t), 3.65 (2H, d), 3.76 (3H, s), 3.95 (2H, d), 5.67 (1H, d), 6.09-6.27 (2H, m), 6.43 (1H, dd), 7.10 (1H, t), 7.30 (1H, s), 7.34-7.45 (1H, m), 8.35 (2H, s), 8.44 (1H, s), 8.81 (1H, d), 8.92 (1H, s), 9.20 (1H, s); m/z: ES+ MH+ 545.5.

Workup

  1. temperaturewas cooled in an ice/water bath
  2. washwashed with brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customPurification by FCC
  6. washeluting with 0-2% 7N methanolic ammonia in CH2Cl2

Sources & evidence

ORD record
ord-c7cbbc51bc53456b8d13eaa83a088833
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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