1,4-Dioxane → HCID 86647860, compound
Reaction equation
[CH3:1][C:2]1([CH3:31])[CH2:11][CH2:10][C:9]2[N:8]=[CH:7][N:6]=[C:5]([N:12]3[CH2:18][C:17]4[CH:19]=[C:20]([C:23]5[CH:24]=[C:25]([NH2:30])[C:26]([NH2:29])=[N:27][CH:28]=5)[CH:21]=[CH:22][C:16]=4[O:15][CH2:14][CH2:13]3)[C:4]=2[CH2:3]1.[N:32]([C:35]([O:37][CH2:38][CH3:39])=[O:36])=[C:33]=S.O1CCOC[CH2:41]1>>[NH2:30][C:25]1[C:26]([NH:29][C:33]([NH:32][C:35](=[O:36])[O:37][CH2:38][CH3:39])=[CH2:41])=[N:27][CH:28]=[C:23]([C:20]2[CH:21]=[CH:22][C:16]3[O:15][CH2:14][CH2:13][N:12]([C:5]4[C:4]5[CH2:3][C:2]([CH3:31])([CH3:1])[CH2:11][CH2:10][C:9]=5[N:8]=[CH:7][N:6]=4)[CH2:18][C:17]=3[CH:19]=2)[CH:24]=1Participants
Procedure
A solution of 5-[4-(6,6-dimethyl-5,6,7,8-tetrahydroquinazolin-4-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl]pyridine-2,3-diamine (188 mg, 0.45 mmol, example 27, step 3) and ethyl isothiocyanatoformate (59 mg, 0.45 mmol) in dioxane (2 mL) was stirred at room temperature for 30 h. After 24 h and 48 h reaction time, additional ethyl isothiocyanatoformate (50 mg, 0.38 mmol) was added each time. The mixture was concentrated and the residue purified directly by column chromatography on silica (ethyl acetate) to give crude ethyl [1-({3-amino-5-[4-(6,6-dimethyl-5,6,7,8-tetrahydroquinazolin-4-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl]pyridine-2-yl}amino)ethenyl]carbamate (82 mg) which was used in the next step without further purification. MS (EI) for C28H33N7O3S: 548 (MH+).
Workup
- additionwas added each time
- concentrationThe mixture was concentrated
- customthe residue purified directly by column chromatography on silica (ethyl acetate)
Sources & evidence
- ORD record
- ord-12222d6b937549d6ac572162ee3f00de
- Source dataset
- uspto-grants-2014_02
- Patent number
- US08648066B2
Reaction notes
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