Diisobutylaluminum hydride → HCID 58456327, compound

HRID 410573Notes

Reaction equation

HRID 410573 reaction equation
[CH:1]1([C:4]2[C:9]([F:10])=[CH:8][N:7]=[C:6]([NH:11][C:12]3[CH:13]=[C:14]([C:19]4[S:23][C:22]([C:24]([OH:34])([C:30]([F:33])([F:32])[F:31])[C:25](OCC)=[O:26])=[N:21][CH:20]=4)[CH:15]=[C:16]([CH3:18])[CH:17]=3)[N:5]=2)[CH2:3][CH2:2]1.CC(C[AlH]CC(C)C)C>O1CCCC1>[CH:1]1([C:4]2[C:9]([F:10])=[CH:8][N:7]=[C:6]([NH:11][C:12]3[CH:13]=[C:14]([C:19]4[S:23][C:22]([C:24]([OH:34])([C:30]([F:33])([F:32])[F:31])[CH2:25][OH:26])=[N:21][CH:20]=4)[CH:15]=[C:16]([CH3:18])[CH:17]=3)[N:5]=2)[CH2:2][CH2:3]1

Participants

4

Reactant 2

HCID 14487Diisobutylaluminum hydrideHCID 67262217HCID 67262217, compound

Product 1

HCID 58456327HCID 58456327, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of ethyl 2-(5-{3-[(4-cyclopropyl-5-fluoropyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-3,3,3-trifluoro-2-hydroxypropanoate (36 mg, 0.073 mmol) in tetrahydrofuran (10 mL) at −78° C. was added DIBAL-H (0.160 mL 0.160 mmol). After 30 minutes, the reaction mixture was warmed to 0° C. After 2 hours, the reaction mixture was quenched with saturated ammonium chloride solution, then diluted with ethyl acetate, washed with brine, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by preparative HPLC Reverse phase (C-18), eluting with acetonitrile/water+0.05% TFA to give 2-(5-{3-[(4-cyclopropyl-5-fluoropyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-3,3,3-trifluoropropane-1,2-diol (3.5 mg, 0.001 mmol, 10%). MS ESI: [M+H]+ m/z 455.1. 1H NMR (500 MHz, DMSO-d6) δ 9.58 (bs, 1H); 8.38 (m, 1H); 8.06 (s, 1H); 7.89 (s, 1H); 7.43 (s, 1H); 7.07 (s, 1H); 3.99 (s, 2H); 2.29 (s, 3H); 2.28-2.23 (m, 1H); 1.18-1.14 (m, 4H). rhSYK activity=+++

Workup

  1. waitAfter 2 hours
  2. customthe reaction mixture was quenched with saturated ammonium chloride solution
  3. additiondiluted with ethyl acetate
  4. washwashed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by preparative HPLC Reverse phase (C-18)
  9. washeluting with acetonitrile/water+0.05% TFA

Sources & evidence

ORD record
ord-9fd9d48040544117a126567fde99e478
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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