1,4-Dioxane → HCID 178491844, compound
Reaction equation
[NH2:1][C:2]1[C:7]([C:8]([C:10]2[C:15]([O:16][CH3:17])=[CH:14][CH:13]=[C:12]([F:18])[C:11]=2[F:19])=[O:9])=[CH:6][N:5]=[C:4]([NH:20][C@H:21]2[CH2:26][CH2:25][C@H:24]([NH2:27])[CH2:23][CH2:22]2)[N:3]=1.C(=O)(O)[O-].[Na+].O1[CH2:38][CH2:37]OCC1>>[NH2:1][C:2]1[C:7]([C:8]([C:10]2[C:15]([O:16][CH3:17])=[CH:14][CH:13]=[C:12]([F:18])[C:11]=2[F:19])=[O:9])=[CH:6][N:5]=[C:4]([NH:20][C@H:21]2[CH2:26][CH2:25][C@H:24]([N:27]3[CH2:38][CH2:37][N:3]([CH3:4])[CH2:2][CH2:7]3)[CH2:23][CH2:22]2)[N:3]=1Participants
Procedure
To a stirred solution of trans-[4-amino-2-(4-amino-cyclohexylamino)-pyrimidin-5-yl]-(2,3-difluoro-6-methoxy-phenyl)-methanone (105 mg, 0.28 mmol, Example 120) and sodium bicarbonate (84 mg, 1 mmol) in 1,4-dioxane (3 mL), bis-2-chloroethyl-methylamine hydrochloride (58 mg, 0.30 mmol, Aldrich) was added and the mixture was stirred at reflux overnight. An additional 20 mg of bis-2-chloroethyl-methylamine hydrochloride (Aldrich) was added and the reaction was refluxed for another 12 hours. The reaction was quenched with water and the mixture was extracted with ethyl acetate (3×10 mL) and the extracts were dried with sodium sulfate. Removal of solvent gave a yellow solid which was chromatographed (8% 9N ammonia in methanol/dichloromethane) to give a pale yellow solid. 16 mg, 12%. MS (ES) MH+=461.
Workup
- temperatureat reflux overnight
- temperaturethe reaction was refluxed for another 12 hours
- customThe reaction was quenched with water
- extractionthe mixture was extracted with ethyl acetate (3×10 mL)
- dry with materialthe extracts were dried with sodium sulfate
- customRemoval of solvent
- customgave a yellow solid which
- customwas chromatographed (8% 9N ammonia in methanol/dichloromethane)
- customto give a pale yellow solid
Sources & evidence
- ORD record
- ord-fcd95032822f49a6ba56f77a92f97654
- Source dataset
- uspto-grants-2009_11
- Patent number
- US07615634B2
Reaction notes
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