Aluminium lithium hydride → tert-Butyl 5-(2-(1-amino-2-methylpropan-2-yl)-pyridin-4-yl)-4-methylthiazol-2-ylcarbamate

HRID 2370375Notes

Reaction equation

HRID 2370375 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[C:7]([O:11][C:12](=[O:31])[NH:13][C:14]1[S:15][C:16]([C:20]2[CH:25]=[CH:24][N:23]=[C:22]([C:26]([C:29]#[N:30])([CH3:28])[CH3:27])[CH:21]=2)=[C:17]([CH3:19])[N:18]=1)([CH3:10])([CH3:9])[CH3:8]>C1COCC1>[C:7]([O:11][C:12](=[O:31])[NH:13][C:14]1[S:15][C:16]([C:20]2[CH:25]=[CH:24][N:23]=[C:22]([C:26]([CH3:28])([CH3:27])[CH2:29][NH2:30])[CH:21]=2)=[C:17]([CH3:19])[N:18]=1)([CH3:8])([CH3:10])[CH3:9]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 59293723Tert-butyl 5-(2-(2-cyanopropan-2-yl)pyridin-4-yl)-4-methylthiazol-2-ylcarbamate

Product 1

HCID 59293724tert-Butyl 5-(2-(1-amino-2-methylpropan-2-yl)-pyridin-4-yl)-4-methylthiazol-2-ylcarbamateYield 43%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

LiAlH4 (1M in THF, 3.06 mL, 3.06 mmol, 1.5 eq) is added to a solution of {5-[2-(cyanodimethyl-methyl)-pyridin-4-yl]-4-methyl-thiazol-2-yl}-carbamic acid tert-butyl ester (Step 21.4) (0.73 g, 2.04 mmol) in THF (10 mL), under an argon atmosphere. The reaction mixture is stirred for 2 h at rt, quenched by addition of H2O (20 mL) and extracted with EtOAc (2×75 mL). The organic phase is washed with a saturated solution of NaHCO3 (2×50 mL), dried (Na2SO4), filtered and concentrated. The residue is purified by silica gel column chromatography (DCM/MeOH/NH3aq, 99:0:1→94:5:1) to afford 318 mg of the title compound as a brown solid: ESI-MS: 363.1 [M+H]+; TLC: Rf=0.11 (DCM/MeOH, 9:1).

Workup

  1. customquenched by addition of H2O (20 mL)
  2. extractionextracted with EtOAc (2×75 mL)
  3. washThe organic phase is washed with a saturated solution of NaHCO3 (2×50 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue is purified by silica gel column chromatography (DCM/MeOH/NH3aq, 99:0:1→94:5:1)

Sources & evidence

ORD record
ord-267c89dcdcdd49e29a3253f80249ac86
Source dataset
uspto-grants-2014_04
Patent number
US08710085B2

Reaction notes

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