Diisopropylethylamine → (R)-ethyl 4-(4-((6-oxo-5,6,6a,7,9,10-hexahydropyrido[3,2-e][1,4]thiazino[4,3-a]pyrazin-3-yl)methyl)piperazin-1-yl)benzoate
Reaction equation
O[CH2:2][C:3]1[CH:12]=[N:11][C:10]2[N:9]3[CH2:13][CH2:14][S:15][CH2:16][C@H:8]3[C:7](=[O:17])[NH:6][C:5]=2[CH:4]=1.[I-].C(C[P+](C)(C)C)#N.CCN(C(C)C)C(C)C.[N:35]1([C:41]2[CH:51]=[CH:50][C:44]([C:45]([O:47][CH2:48][CH3:49])=[O:46])=[CH:43][CH:42]=2)[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1>C(#N)CC.CCO.O>[O:17]=[C:7]1[NH:6][C:5]2[CH:4]=[C:3]([CH2:2][N:38]3[CH2:37][CH2:36][N:35]([C:41]4[CH:42]=[CH:43][C:44]([C:45]([O:47][CH2:48][CH3:49])=[O:46])=[CH:50][CH:51]=4)[CH2:40][CH2:39]3)[CH:12]=[N:11][C:10]=2[N:9]2[CH2:13][CH2:14][S:15][CH2:16][C@@H:8]12Participants
8
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 90 °C
Procedure
To a suspension of (R)-3-(hydroxymethyl)-6a,7,9,10-tetrahydropyrido[3,2-e][1,4]thiazino[4,3-a]pyrazin-6(5H)-one (333 mg, 1.325 mmol) in propiononitrile (3313 μl) was added (cyanomethyl)trimethylphosphonium iodide (386 mg, 1.590 mmol) and DIPEA (694 μl, 3.98 mmol) and finally ethyl 4-(piperazin-1-yl)benzoate (310 mg, 1.325 mmol). The vial was heated to 90° C. for 12 hours. The reaction was then cooled to room temperature, diluted with EtOH (8 ml) and water (1 mL), then filtered. The precipitate was filtered off and dried in vacuum to afford the title compound 508 mg, 82%) as a white solid. [M+H] calc'd for C, 24; H, 29; N, 5; O, 3; S, 468; found, 468.
Workup
- temperatureThe reaction was then cooled to room temperature
- filtrationfiltered
- filtrationThe precipitate was filtered off
- customdried in vacuum
Sources & evidence
- ORD record
- ord-2122c49fd5aa4bbfa5d33c2622a04de9
- Source dataset
- uspto-grants-2013_05
- Patent number
- US08450323B2
Reaction notes
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