Hydroxylamine → (S)-2-(6-(5-Methylpyridin-2-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-ylamino)-2-(4-(trifluoromethyl)phenyl)ethanol

HRID 241879Notes

Reaction equation

HRID 241879 reaction equation
Cl[C:2]1[C:3]2[CH2:11][N:10]([C:12]3[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][N:13]=3)[CH2:9][CH2:8][C:4]=2[N:5]=[CH:6][N:7]=1.[NH2:19][C@@H:20]([C:23]1[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=1)[CH2:21][OH:22].C(N(CC)C(C)C)(C)C.NO.C([O-])([O-])=O.[Na+].[Na+]>C(#N)C.CCOC(C)=O>[CH3:18][C:15]1[CH:16]=[CH:17][C:12]([N:10]2[CH2:9][CH2:8][C:4]3[N:5]=[CH:6][N:7]=[C:2]([NH:19][C@@H:20]([C:23]4[CH:24]=[CH:25][C:26]([C:29]([F:30])([F:31])[F:32])=[CH:27][CH:28]=4)[CH2:21][OH:22])[C:3]=3[CH2:11]2)=[N:13][CH:14]=1

Participants

8

Reactant 5

HCID 787HydroxylamineHCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 10584357(S)-2-Amino-2-(4-(trifluoromethyl)phenyl)ethanolHCID 593464574-Chloro-5,6,7,8-tetrahydro-6-(5-methylpyridin-2-yl)pyrido[4,3-d]pyrimidine

Product 1

HCID 25032423(S)-2-(6-(5-Methylpyridin-2-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-ylamino)-2-(4-(trifluoromethyl)phenyl)ethanol

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A reaction mixture of 4-chloro-5,6,7,8-tetrahydro-6-(5-methylpyridin-2-yl)pyrido[4,3-d]pyrimidine (150 mg, 0.58 mmol) and (S)-2-amino-2-(4-(trifluoromethyl)phenyl)ethanol (180 mg, 0.86 mmol) in acetonitrile (3 mL) and N,N-diisopropylethylamine (0.20 mL, 1.2 mmol) was run in a microwave reactor at 180° C. for 2 h. LC-MS indicated amino alcohol was consumed and about 50% conversion of the chloride. Additional (S)-2-amino-2-(4-(trifluoromethyl)phenyl)ethanol (100 mg) was added and the mixture was run microwave reaction at 160° C. for another 2 h. The reaction mixture was treated with aq. Na2CO3 and EtOAc (150 mL). The organic layer was separated and washed with brine, dried (Na2SO4), and concentrated. The residue was purified by semi-prep HPLC to give a white powder.

Workup

  1. customwas consumed
  2. additionAdditional (S)-2-amino-2-(4-(trifluoromethyl)phenyl)ethanol (100 mg) was added
  3. custommicrowave reaction at 160° C. for another 2 h
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe residue was purified by semi-prep HPLC
  9. customto give a white powder

Sources & evidence

ORD record
ord-399681aeb9014a1caf21ccdc86eec4e6
Source dataset
uspto-grants-2014_02
Patent number
US08653091B2

Reaction notes

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