Triethylamine → HCID 86709287, compound

HRID 517303Notes

Reaction equation

HRID 517303 reaction equation
[CH3:1][C@H:2]1[CH2:7][CH2:6][CH:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[S:4](=[O:15])(=[O:14])[N:3]1[CH2:16][C:17]1[CH:25]=[CH:24][C:20]([C:21]([OH:23])=O)=[CH:19][CH:18]=1.[O:26]1[CH2:31][CH2:30][CH:29]([NH2:32])[CH2:28][CH2:27]1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C)C=O>[CH3:1][C@H:2]1[CH2:7][CH2:6][CH:5]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[S:4](=[O:15])(=[O:14])[N:3]1[CH2:16][C:17]1[CH:18]=[CH:19][C:20]([C:21]([NH:32][CH:29]2[CH2:30][CH2:31][O:26][CH2:27][CH2:28]2)=[O:23])=[CH:24][CH:25]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 4192234-AminotetrahydropyranHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86709288HCID 86709288, compound

Product 1

HCID 86709287HCID 86709287, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-[[(3S)-3-methyl-1,1-dioxo-6-phenyl-thiazinan-2-yl]methyl]benzoic acid Stereoisomer A (75 mg, 0.21 mmol), tetrahydropyran-4-amine (64 mg, 0.63 mmol) and triethylamine (0.12 mL, 0.83 mmol) in N,N-dimethylformamide (1.5 mL) was added O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (121 mg, 0.31 mmol) and the reaction was stirred at room temperature for 2 hours. The reaction was then partitioned between dichloromethane and saturated sodium bicarbonate in water. The organic layer was separated, concentrated and purified by preparative HPLC to give 4-(((3S)-3-methyl-1,1-dioxido-6-phenyl-1,2-thiazinan-2-yl)methyl)-N-(tetrahydro-2H-pyran-4-yl)benzamide Stereoisomer A (66.4 mg, 0.15 mmol, 72% yield). 1H NMR (400 MHz, DMSO) δ 8.27-8.19 (d, J=7.7 Hz, 1H), 7.85-7.77 (m, 2H), 7.50-7.43 (m, 4H), 7.43-7.34 (m, 3H), 4.64-4.53 (m, 1H), 4.47-4.33 (m, 2H), 4.18-4.06 (m, 1H), 4.06-3.93 (m, 1H), 3.91-3.81 (m, 2H), 3.46-3.33 (m, 2H), 2.48-2.37 (m, 1H), 2.17-2.08 (m, 1H), 1.92-1.69 (m, 3H), 1.70-1.50 (m, 3H), 1.11-1.02 (d, J=6.9 Hz, 3H); LCMS [M+1]+=443.2.

Workup

  1. customThe reaction was then partitioned between dichloromethane and saturated sodium bicarbonate in water
  2. customThe organic layer was separated
  3. concentrationconcentrated
  4. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-845ee6fe8f2647cf924cf930f6dfded1
Source dataset
uspto-grants-2015_08
Patent number
US09115101B2

Reaction notes

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