Tetrahydrofuran → H3b-6527

HRID 58139Notes

Reaction equation

HRID 58139 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH3:15])[CH2:10][CH2:9]2)[CH:5]=[CH:4][C:3]=1[NH:16][C:17]1[N:22]=[CH:21][N:20]=[C:19]([N:23]([CH3:39])[C:24]([NH:26][C:27]2[C:32]([Cl:33])=[C:31]([O:34][CH3:35])[CH:30]=[C:29]([O:36][CH3:37])[C:28]=2[Cl:38])=[O:25])[CH:18]=1.[C:40](Cl)(=[O:43])[CH:41]=[CH2:42].C1COCC1>CO>[Cl:38][C:28]1[C:29]([O:36][CH3:37])=[CH:30][C:31]([O:34][CH3:35])=[C:32]([Cl:33])[C:27]=1[NH:26][C:24](=[O:25])[N:23]([C:19]1[N:20]=[CH:21][N:22]=[C:17]([NH:16][C:3]2[CH:4]=[CH:5][C:6]([N:8]3[CH2:9][CH2:10][N:11]([CH2:14][CH3:15])[CH2:12][CH2:13]3)=[CH:7][C:2]=2[NH:1][C:40](=[O:43])[CH:41]=[CH2:42])[CH:18]=1)[CH3:39]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 13140Acryloyl chlorideHCID 1180245461-(6-((2-Amino-4-(4-ethylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)-3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylurea

Product 1

HCID 118029202H3b-6527Yield 7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 1-(6-(2-amino-4-(4-ethylpiperazin-1-yl)phenylamino)pyrimidin-4-yl)-3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylurea (280 mg, purity: 90%, 0.44 mmol) in THE (30 mL) was added a solution of acryloyl chloride in THF (20 mg/mL, 2 mL, 0.44 mmol) at −10° C., and the resulting mixture was stirred for 1 hour at this temperature. MeOH (1 mL) was added to quench the reaction. The mixture was concentrated and the residue was purified by prep-HPLC and prep-TLC to obtain the title compound (20 mg, yield: 7%). 1H NMR (400 MHz, CDCl3) δ 1.31 (t, 3H), 2.65 (q, 2H), 2.62-2.68 (m, 4H), 3.27 (s, 3H), 3.36-3.38 (m, 4H), 3.91 (s, 6H), 5.76 (d, 1H), 5.90 (s, 1H), 6.24 (dd, 1H), 6.41 (d, 1H), 6.52 (s, 1H), 6.74 (dd, 1H), 7.07 (br s, 1H), 7.23 (d, 1H), 7.72 (br s, 1H), 7.98 (br s, 1H), 8.37 (s, 1H), 12.52 (s, 1H); MS (ESI): 629 [M+H]+.

Workup

  1. customto quench
  2. customthe reaction
  3. concentrationThe mixture was concentrated
  4. customthe residue was purified by prep-HPLC and prep-TLC

Sources & evidence

ORD record
ord-edc2c2a1091248d5bf546dc4c8280ccf
Source dataset
uspto-grants-2016_09
Patent number
US09434697B2

Reaction notes

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