N,N-Dimethylglycine → HCID 86709279, compound

HRID 517299Notes

Reaction equation

HRID 517299 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[C@@H:14]([CH3:15])[CH2:13][CH2:12][CH:11]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[S:10]2(=[O:23])=[O:22])=[C:4]([F:24])[CH:3]=1.Cl.[N:26]1[N:27]=[CH:28][N:29]([CH:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)[CH:30]=1.CN(C)CC(O)=O.C([O-])(=O)CC([O-])=O.C([P+](CCCC)(CCCC)CCCC)CCC.C([P+](CCCC)(CCCC)CCCC)CCC>>[F:24][C:4]1[CH:3]=[C:2]([N:34]2[CH2:33][CH2:32][CH:31]([N:29]3[CH:30]=[N:26][N:27]=[CH:28]3)[CH2:36][CH2:35]2)[CH:7]=[CH:6][C:5]=1[CH2:8][N:9]1[C@@H:14]([CH3:15])[CH2:13][CH2:12][CH:11]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[S:10]1(=[O:23])=[O:22]

Participants

5

Reactant 4

HCID 673N,N-DimethylglycineHCID 44473435Bis(tetrabutylphosphanium) propanedioateHCID 755304451609407-68-2HCID 86709280HCID 86709280, compound

Product 1

HCID 86709279HCID 86709279, compoundYield 37%

Conditions

Temperature
45 °C

Procedure

A vial was charged with (3S)-2-[(4-bromo-2-fluoro-phenyl)methyl]-3-methyl-6-phenyl-thiazinane 1,1-dioxide (250 mg, 0.61 mmol), 4-(1,2,4-triazol-4-yl)piperidine hydrochloride (172 mg, 0.91 mmol), cuprous iodide (35 mg, 0.18 mmol), N,N-dimethylglycine (38 mg, 0.36 mmol) and tetrabutylphosphonium malonate (1.3 g, 1.9 mmol) and the vial was purged with nitrogen for. Dimethyl sulfoxide (3 mL) was then added and the vial was purged with nitrogen for an additional 2 minutes. The reaction mixture was then sonicated for 5 minutes and stirred at 45° C. for 20 hours. The DMSO solution was then directly purified by preparative HPLC to give (3S)-2-[[2-fluoro-4-[4-(1,2,4-triazol-4-yl)-1-piperidyl]phenyl]methyl]-3-methyl-6-phenyl-thiazinane 1,1-dioxide Stereoisomer A (109 mg, 0.23 mmol, 37% yield) as a white solid. 1H NMR (400 MHz, DMSO) δ 8.66-8.62 (s, 2H), 7.49-7.43 (m, 2H), 7.43-7.29 (m, 4H), 6.87-6.82 (m, 1H), 6.80-6.73 (m, 1H), 4.49-4.24 (m, 4H), 4.15-4.04 (m, 1H), 3.90-3.80 (m, 2H), 2.89-2.77 (m, 2H), 2.47-2.35 (m, 1H), 2.15-2.04 (m, 3H), 2.04-1.89 (m, 2H), 1.88-1.74 (m, 1H), 1.70-1.60 (m, 1H), 1.14-1.05 (d, J=6.9 Hz, 3H); LCMS [M+1]+=484.2.

Workup

  1. customthe vial was purged with nitrogen for
  2. additionDimethyl sulfoxide (3 mL) was then added
  3. customthe vial was purged with nitrogen for an additional 2 minutes
  4. customThe reaction mixture was then sonicated for 5 minutes
  5. customThe DMSO solution was then directly purified by preparative HPLC

Sources & evidence

ORD record
ord-41347df2d4ff484087a8fce6acbb8ae9
Source dataset
uspto-grants-2015_08
Patent number
US09115101B2

Reaction notes

Loading…