Acetic Acid → (R)-N-{dicyclopropyl[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]methyl}-2-methylpropane-2-sulfinamide

HRID 1039988Notes

Reaction equation

HRID 1039988 reaction equation
C([N-]C(C)C)(C)C.[Li+].[CH3:9][C:10]1[CH:11]=[C:12]([NH:21][C:22]2[N:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][N:23]=2)[CH:13]=[C:14]([C:16]2[S:20][CH:19]=[N:18][CH:17]=2)[CH:15]=1.[CH:32]1([C:35]([CH:43]2[CH2:45][CH2:44]2)=[N:36][S@@:37]([C:39]([CH3:42])([CH3:41])[CH3:40])=[O:38])[CH2:34][CH2:33]1.C(O)(=O)C>O1CCCC1>[CH:43]1([C:35]([CH:32]2[CH2:34][CH2:33]2)([C:19]2[S:20][C:16]([C:14]3[CH:13]=[C:12]([NH:21][C:22]4[N:27]=[C:26]([C:28]([F:29])([F:31])[F:30])[CH:25]=[CH:24][N:23]=4)[CH:11]=[C:10]([CH3:9])[CH:15]=3)=[CH:17][N:18]=2)[NH:36][S@@:37]([C:39]([CH3:41])([CH3:42])[CH3:40])=[O:38])[CH2:45][CH2:44]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 2724682Lithium diisopropylamideHCID 58456403N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine2×HCID 86658247(R)-N-(dicyclopropylmethylidene)-2-methylpropane-2-sulfinamide

Product 1

HCID 67432173(R)-N-{dicyclopropyl[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]methyl}-2-methylpropane-2-sulfinamideYield 76.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of lithium diisopropylamide (1.8 M, 2.12 mL, 3.81 mmol) in tetrahydrofuran (5 mL) at −78° C. was added a solution of N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (Intermediate 24, 564 mg, 1.68 mmol) in tetrahydrofuran (5 mL) over 8 minutes. After 40 minutes, a solution of (R)—N-(dicyclopropylmethylidene)-2-methylpropane-2-sulfinamide (0.325 g, 1.52 mmol) in tetrahydrofuran (4 mL) was added all at once. After 90 minutes, acetic acid (0.275 mL) was added and the reaction mixture was partitioned between ethyl acetate (45 mL) and saturated aqueous sodium bicarbonate solution (20 mL). The layers were separated and the organic layer was washed with brine (20 mL), dried over sodium sulfate, filtered, and concentrated. Purification of the crude material using silica gel flash chromatography (ethyl acetate/hexanes) yielded (R)—N-{dicyclopropyl[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]methyl}-2-methylpropane-2-sulfinamide (638.6 mg, 1.16 mmol, 76% yield) as a yellow film. MS ESI: [M H] m/z 550.1.

Workup

  1. waitAfter 90 minutes
  2. customthe reaction mixture was partitioned between ethyl acetate (45 mL) and saturated aqueous sodium bicarbonate solution (20 mL)
  3. customThe layers were separated
  4. washthe organic layer was washed with brine (20 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification of the crude material

Sources & evidence

ORD record
ord-beebe9b323af4b5899f4a39c155e7b71
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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