2-(1-(tert-butyldiphenylsilyloxy)ethyl)-N-((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)thiazole-4-carboxamide → N-((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-(1-hydroxyethyl)thiazole-4-carboxamide

HRID 872861Notes

Reaction equation

HRID 872861 reaction equation
[Si]([O:18][CH:19]([C:21]1[S:22][CH:23]=[C:24]([C:26]([NH:28][C@@H:29]([CH3:45])[CH2:30][N:31]2[CH:35]=[CH:34][C:33]([C:36]3[CH:41]=[CH:40][C:39]([C:42]#[N:43])=[C:38]([Cl:44])[CH:37]=3)=[N:32]2)=[O:27])[N:25]=1)[CH3:20])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1>C1COCC1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:44][C:38]1[CH:37]=[C:36]([C:33]2[CH:34]=[CH:35][N:31]([CH2:30][C@@H:29]([NH:28][C:26]([C:24]3[N:25]=[C:21]([CH:19]([OH:18])[CH3:20])[S:22][CH:23]=3)=[O:27])[CH3:45])[N:32]=2)[CH:41]=[CH:40][C:39]=1[C:42]#[N:43]

Participants

4

Reactant 1

HCID 706541322-(1-(tert-butyldiphenylsilyloxy)ethyl)-N-((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)thiazole-4-carboxamide

Product 1

HCID 70655948N-((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-(1-hydroxyethyl)thiazole-4-carboxamide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 2724141Tetrabutylammonium FluorideSolvent2×

Procedure

2-(1-(tert-butyldiphenylsilyloxy)ethyl)-N—((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)thiazole-4-carboxamide (264 mg, 0.403 mmol) dissolved in THF (20 ml) and tetrabutylammonium fluoride, 1.0 M solution in THF (0.41 ml, 0.410 mmol), were added into a flask and stirred at RT overnight. After reacting for an hour, more of tetrabutylammonium fluoride, 1.0 M solution in THF (0.41 ml, 0.410 mmol), was added. The crude product was dried by evaporating and extracted with DCM/water. The organic phase was isolated with phase separator and evaporated. The product was purified by flash chromatography and recrystallization from ethyl acetate/heptane, respectively. 1H-NMR (400 MHz; DMSO-d6): δ 1.10-1.15 (m, 3H), 1.46 (t, 3H), 4.29-4.52 (m, 3H), 4.93-5.01 (m, 1H), 6.24 (s, 1H), 6.94-6.98 (m, 1H), 7.83-7.87 (m, 1H), 7.92-8.00 (m, 2H), 8.08 (s, 1H), 8.10 (d, 1H), 8.33-8.39 (m, 1H).

Workup

  1. additionwas added
  2. dry with materialThe crude product was dried
  3. customby evaporating
  4. extractionextracted with DCM/water
  5. customThe organic phase was isolated with phase separator
  6. customevaporated
  7. customThe product was purified by flash chromatography and recrystallization from ethyl acetate/heptane

Sources & evidence

ORD record
ord-258d9c09fb0b49aa8b83a2e5d49c47ca
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

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