Aluminium lithium hydride → Tert-butyl (3-((5-(hydroxymethyl)-2-(methylthio)pyrimidin-4-yl)amino)phenyl)carbamate

HRID 527393Notes

Reaction equation

HRID 527393 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[C:11]([NH:15][C:16]2[C:21]([C:22](OCC)=[O:23])=[CH:20][N:19]=[C:18]([S:27][CH3:28])[N:17]=2)[CH:12]=[CH:13][CH:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[OH:23][CH2:22][C:21]1[C:16]([NH:15][C:11]2[CH:10]=[C:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])[CH:14]=[CH:13][CH:12]=2)=[N:17][C:18]([S:27][CH3:28])=[N:19][CH:20]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 57343535Ethyl 4-((3-((tert-butoxycarbonyl)amino)phenyl)amino)-2-(methylthio)pyrimidine-5-carboxylate

Product 1

HCID 57343536Tert-butyl (3-((5-(hydroxymethyl)-2-(methylthio)pyrimidin-4-yl)amino)phenyl)carbamateYield 92%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of ethyl 4-((3-((tert-butoxycarbonyl)amino)phenyl)amino)-2-(methylthio)pyrimidine-5-carboxylate (50c) (340 g, 0.84 mol) in THF (200 mL) at −40° C. was added LiAlH4 (2.57 L of 1.0 M solution in THF, 2.57 mol) dropwise. The reaction mixture was stirred at 0° C. for 13 h, then cooled to −20° C. and carefully quenched with solid Na2SO4.10H2O. The reaction mixture was filtered and rinsed with 2×150 mL of EtOAc. The filtrate was concentrated affording crude tert-butyl (3-((5-(hydroxymethyl)-2-(methylthio)pyrimidin-4-yl)amino)phenyl)carbamate (50d) (280 g, 92% yield). m/z (ESI, +ve ion) 363.0 (M+1)+.

Workup

  1. temperaturecooled to −20° C.
  2. customcarefully quenched with solid Na2SO4.10H2O
  3. filtrationThe reaction mixture was filtered
  4. washrinsed with 2×150 mL of EtOAc
  5. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-550b8bbfaf3c430c901a2e7af4bd4cb1
Source dataset
uspto-grants-2016_05
Patent number
US09346801B2

Reaction notes

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