Acryloyl chloride → HCID 86677247, compound

HRID 1842624Notes

Reaction equation

HRID 1842624 reaction equation
[C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[NH2:6][C:7]1[C:8]([N:33]2[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]2)=[CH:9][C:10]([O:31][CH3:32])=[C:11]([NH:13][C:14]2[N:19]=[C:18]([C:20]3[CH:21]=[N:22][N:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=34)[C:17]([C:29]#[N:30])=[CH:16][N:15]=2)[CH:12]=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:29]([C:17]1[C:18]([C:20]2[CH:21]=[N:22][N:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=23)=[N:19][C:14]([NH:13][C:11]2[C:10]([O:31][CH3:32])=[CH:9][C:8]([N:33]3[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]3)=[C:7]([NH:6][C:1](=[O:4])[CH:2]=[CH2:3])[CH:12]=2)=[N:15][CH:16]=1)#[N:30]

Participants

5

Reactant 3

HCID 13140Acryloyl chloride2×HCID 81531DiisopropylethylamineHCID 86677248HCID 86677248, compound2×

Product 1

HCID 86677247HCID 86677247, compoundYield 69.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of acryloyl chloride (0.017 mL, 0.21 mmol) in CH2Cl2 (0.6 mL) was added to a mixture of 2-{[5-amino-2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]amino}-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidine-5-carbonitrile (Intermediate 65, 87 mg, 0.19 mmol) and DIPEA (0.063 mL, 0.38 mmol) in CH2Cl2 (1.5 mL) at 0° C. The mixture was then stirred at 0° C. for 4 h. (during this time a further 0.5 eq acryloyl chloride was added). The mixture was then diluted with CH2Cl2, washed twice with sat. NaHCO3, then with water, and then dried (MgSO4). Purification by FCC, eluting with 0-6% methanolic ammonia in CH2Cl2 gave the title compound (67 mg, 69%) as a yellow solid; 1H NMR: (102° C.) 2.30 (3H, s), 2.56-2.59 (4H, m), 2.93-2.96 (4H, m), 3.78 (3H, s), 5.67-5.7 (1H, m), 6.16 (1H, d), 6.44-6.51 (1H, m), 6.95 (1H, s), 7.11 (1H, t), 7.35 (1H, t), 8.20 (1H, s), 8.32 (1H, d), 8.66 (1H, s), 8.72 (1H, br s), 8.76 (1H, d), 8.91 (1H, s), 8.96 (1H, br s); m/z: ES+ MH+ 510.5.

Workup

  1. additionwas added)
  2. washwashed twice with sat. NaHCO3
  3. dry with materialwith water, and then dried (MgSO4)
  4. customPurification by FCC
  5. washeluting with 0-6% methanolic ammonia in CH2Cl2

Sources & evidence

ORD record
ord-3fbc9596cc5e4fc790225fa2a0e871ef
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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