Acryloyl chloride → HCID 118029203, compound

HRID 58150Notes

Reaction equation

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

Participants

Conditions

Temperature: -10 °C

Procedure

To a stirred solution of 1-[6-(2-amino-4-dimethylaminomethyl-phenylamino)-pyrimidin-4-yl]-3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-methyl-urea (45 g, 0.11 mmol) in THF (40 mL) at −10° C. was added acryloyl chloride (30 g, 0.33 mmol) in THF (3 mL). The solution was stirred at −10° C. for 5 hours. LCMS showed major product peak. The reaction was quenched with MeOH (3 mL) and evaporated. The residue was purified by prep-HPLC (water/ACN in NH4HCO3 condition) to afford the title compound (6 mg, yield: 15%). 1H-NMR (400 MHz, MeOH-d4) δ 8.25 (s, 1H), 7.47 (d, 1H), 7.44 (s, 1H), 7.16 (dd, 1H), 6.70 (s, 1H), 6.33-6.20 (m, 3H), 5.67 (dd, 1H), 3.84 (s, 6H), 3.43 (s, 2H) 3.22 (s, 3H), 2.20 (s, 6H); MS (ESI): 574 [M+H]+.

Workup

customThe reaction was quenched with MeOH (3 mL)
customevaporated
customThe residue was purified by prep-HPLC (water/ACN in NH4HCO3 condition)

Sources & evidence

ORD record: ord-476aec9a794c49f696e03d74ae5ac0b8
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09434697B2

Reaction notes

Loading…