Dimethyl Sulfoxide → HCID 178428316, compound

HRID 928139Notes

Reaction equation

HRID 928139 reaction equation
[OH:1][C:2]([C@H:27]1[CH2:32][CH2:31][C@H:30]([C:33]#[N:34])[CH2:29][CH2:28]1)([C:4]1[S:5][C:6]([C:9]2[CH:14]=[C:13]([NH:15][C:16]3[N:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][N:17]=3)[CH:12]=[C:11]([CH3:26])[CH:10]=2)=[CH:7][N:8]=1)[CH3:3].[N-:35]=[N+:36]=[N-:37].[Na+].CS(C)=[O:41].CN([CH:46]=[O:47])C>O.[Br-].[Zn+2].[Br-]>[F:23][C:22]([F:25])([F:24])[C:46]([O-:47])=[O:41].[OH:1][C:2]([C:4]1[S:5][C:6]([C:9]2[CH:14]=[C:13]([NH:15][C:16]3[N:21]=[C:20]([C:22]([F:24])([F:23])[F:25])[CH:19]=[CH:18][NH+:17]=3)[CH:12]=[C:11]([CH3:26])[CH:10]=2)=[CH:7][N:8]=1)([C@H:27]1[CH2:28][CH2:29][C@H:30]([C:33]2[N:35]=[N:36][NH:37][N:34]=2)[CH2:31][CH2:32]1)[CH3:3]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 6228DimethylformamideHCID 33557Sodium AzideHCID 178428304HCID 178428304, compound

Product 1

HCID 178428316HCID 178428316, compound

Reagents, catalysts & solvents 2

HCID 10421208Zinc bromideCatalystHCID 962WaterSolvent

Procedure

To a solution of trans-4-{1-hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}cyclohexanecarbonitrile (214 mg, 0.439 mmol) in DMF (4.4 mL) was added zinc bromide (99 mg, 0.439 mmol) and sodium azide (29 mg, 0.439 mmol) and the reaction was heated overnight to 130° C. The reaction was then cooled to room temperature and diluted with a small amount of water. DMSO (2 mL) was added and the solution was purified by reverse phase HPLC to afford racemic 2-{[3-(2-{1-hydroxy-1-[trans-4-(2H-tetrazol-5-yl)cyclohexyl]ethyl}-1,3-thiazol-5-yl)-5-methylphenyl]amino}-4-(trifluoromethyl)pyrimidin-1-ium trifluoroacetate. The enantiomers were separated by supercritical fluid chromatography (chiral OJ column, 2:8 methanol/CO2 with a 12 minute run time) to yield 2-{[3-(2-{(1R)-1-hydroxy-1-[trans-4-(2H-tetrazol-5-yl)cyclohexyl]ethyl}-1,3-thiazol-5-yl)-5-methylphenyl]amino}-4-(trifluoromethyl)pyrimidin-1-ium trifluoroacetate and 2-{[3-(2-{(1S)-1-hydroxy-1-[trans-4-(2H-tetrazol-5-yl)cyclohexyl]ethyl}-1,3-thiazol-5-yl)-5-methylphenyl]amino}-4-(trifluoromethyl)pyrimidin-1-ium trifluoroacetate. Characterization for the faster eluting enantiomer (Rt=6.38 min): MS ESI calc'd. for C24H27F3N8OS [M+H]+531. found 531. 1H NMR (500 MHz, DMSO-d6) δ 10.25 (s, 1H), 8.83 (d, J=4.9, 1H), 7.99-7.94 (m, 2H), 7.46 (s, 1H), 7.27 (d, J=4.9, 1H), 7.15 (s, 1H), 5.90 (s, 1H), 2.90-2.71 (m, 1H), 2.31 (s, 3H), 2.13-1.88 (m, 3H), 1.83-1.67 (m, 1H), 1.67-1.56 (m, 1H), 1.51 (s, 3H), 1.47-1.31 (m, 3H), 1.29-1.09 (m, 1H). rhSyk=+++. rhSyk (slower eluting enantiomer, Rt=8.71 min)=+++

Workup

  1. temperaturethe reaction was heated overnight to 130° C
  2. customthe solution was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-a8fc177df4d2473ba79b4cda690ddd55
Source dataset
uspto-grants-2016_03
Patent number
US09290490B2

Reaction notes

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