Triethylamine → HCID 86658254, compound

HRID 410657Notes

Reaction equation

HRID 410657 reaction equation
C(N(CC)CC)C.[OH:8][C@:9]1([C:21]2[S:22][C:23]([C:26]3[CH:31]=[C:30]([NH:32][C:33]4[N:38]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:36]=[CH:35][N:34]=4)[CH:29]=[C:28]([CH2:43][OH:44])[CH:27]=3)=[CH:24][N:25]=2)[CH2:14][CH2:13][C@H:12]([C:15]([O:17][CH3:18])=[O:16])[C:11]([CH3:20])([CH3:19])[CH2:10]1.[CH3:45][S:46](Cl)(=[O:48])=[O:47]>ClCCl>[OH:8][C@:9]1([C:21]2[S:22][C:23]([C:26]3[CH:31]=[C:30]([NH:32][C:33]4[N:38]=[C:37]([C:39]([F:41])([F:42])[F:40])[CH:36]=[CH:35][N:34]=4)[CH:29]=[C:28]([CH2:43][O:44][S:46]([CH3:45])(=[O:48])=[O:47])[CH:27]=3)=[CH:24][N:25]=2)[CH2:14][CH2:13][C@H:12]([C:15]([O:17][CH3:18])=[O:16])[C:11]([CH3:20])([CH3:19])[CH2:10]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 67431335HCID 67431335, compound

Product 1

HCID 86658254HCID 86658254, compoundYield 88.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
23 °C

Procedure

Triethylamine (0.200 ml, 1.434 mmol, 1.5 equiv) was added to a stirring solution of methyl (1S,4R)-4-hydroxy-4-{5-[3-(hydroxymethyl)-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl]-1,3-thiazol-2-yl}-2,2-dimethylcyclohexanecarboxylate (513 mg, 0.956 mmol) in anhydrous dichloromethane (15 mL). The orange solution was cooled to 0° C. (water/ice) then charged with methanesulfonyl chloride (0.089 ml, 1.147 mmol, 1.2 equiv). The reaction mixture was allowed to slowly warm to 23° C. and stir for 5 d. The mixture was partitioned between methylene chloride (2×90 ml) and water (95 ml). The combined organic layers were dried over Na2SO4, filtered and concentrated to afford methyl (1S,4R)-4-hydroxy-2,2-dimethyl-4-[5-(3-{[(methylsulfonyl)oxy]methyl}-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclohexanecarboxylate (520 mg, 71%), as an orange-yellow oil. 1H NMR (500 MHz, CDCl3) δ 8.79 (bs, 1H), 8.66 (d, J=4.9 Hz, 1H), 7.95 (s, 1H), 7.85 (s, 1H), 7.61 (s, 1H), 7.23 (s, 1H), 7.06 (d, J=4.9 Hz, 1H), 4.59 (s, 1H), 3.90 (s, 2H), 3.69 (s, 3H), 3.01 (s, 2H), 2.38-2.25 (m, 2H), 2.01 (m, 3H), 1.95-1.77 (m, 4H), 1.35-1.20 (m, 6H).

Workup

  1. customThe mixture was partitioned between methylene chloride (2×90 ml) and water (95 ml)
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-179d76d9b28b437f8bab69324fec7fe8
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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