Tetrahydrofuran → Olmutinib

HRID 1850016Notes

Reaction equation

[NH2:1][C:2]1[CH:3]=[C:4]([CH:29]=[CH:30][CH:31]=1)[O:5][C:6]1[C:7]2[S:28][CH:27]=[CH:26][C:8]=2[N:9]=[C:10]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]3)=[CH:15][CH:14]=2)[N:11]=1.C([O-])(O)=O.[Na+].[O:37]1C[CH2:40][CH2:39][CH2:38]1.C(Cl)(=O)C=C>O>[CH3:25][N:22]1[CH2:21][CH2:20][N:19]([C:16]2[CH:15]=[CH:14][C:13]([NH:12][C:10]3[N:11]=[C:6]([O:5][C:4]4[CH:3]=[C:2]([NH:1][C:38](=[O:37])[CH:39]=[CH2:40])[CH:31]=[CH:30][CH:29]=4)[C:7]4[S:28][CH:27]=[CH:26][C:8]=4[N:9]=3)=[CH:18][CH:17]=2)[CH2:24][CH2:23]1

Participants

Conditions

Temperature: 0 °C

Procedure

The compound (3.69 mmol) obtained in Step 5 and NaHCO3 (11.07 mmol) were distilled with tetrahydrofuran (40 mL) and distilled water (6 mL), and acryloyl chloride (3.69 mmol) was added thereto slowly at 0° C. with stirring for 15 min. After the reaction was complete, the reaction mixture was distilled with dichloromethane and then washed with sat. NaHCO3 aqueous solution. The organic layer was dried with anhydrous sodium sulfate and then filtered and distilled under a reduced pressure, and the residue was separated by column chromatography (chloroform:methanol=20:1 (volume ratio)) to obtain the title compound (yield: 68.2%).

Workup

additionwas added
distillationthe reaction mixture was distilled with dichloromethane
washwashed with sat. NaHCO3 aqueous solution
dry with materialThe organic layer was dried with anhydrous sodium sulfate
filtrationfiltered
distillationdistilled under a reduced pressure
customthe residue was separated by column chromatography (chloroform:methanol=20:1 (volume ratio))

Sources & evidence

ORD record: ord-6b19e0f275e14cf5b739d54b97efd947
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08957065B2

Reaction notes

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