Diisopropylethylamine → 2-{4-[(S)-2-Hydroxy-1-(6-trifluoromethyl-pyridin-3-yl)-ethylamino]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl}-5-methyl-benzonitrile

HRID 657802Notes

Reaction equation

HRID 657802 reaction equation
Cl[C:2]1[C:3]2[CH2:11][N:10]([C:12]3[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][C:13]=3[C:14]#[N:15])[CH2:9][CH2:8][C:4]=2[N:5]=[CH:6][N:7]=1.[NH2:21][C@@H:22]([C:25]1[CH:26]=[N:27][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:29][CH:30]=1)[CH2:23][OH:24].C(N(CC)C(C)C)(C)C>C(#N)C>[OH:24][CH2:23][C@@H:22]([NH:21][C:2]1[C:3]2[CH2:11][N:10]([C:12]3[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][C:13]=3[C:14]#[N:15])[CH2:9][CH2:8][C:4]=2[N:5]=[CH:6][N:7]=1)[C:25]1[CH:26]=[N:27][C:28]([C:31]([F:32])([F:33])[F:34])=[CH:29][CH:30]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 58188187(S)-2-amino-2-(6-(trifluoromethyl)pyridin-3-yl)ethanolHCID 598406882-(4-Chloro-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-5-methylbenzonitrile

Product 1

HCID 250595442-{4-[(S)-2-Hydroxy-1-(6-trifluoromethyl-pyridin-3-yl)-ethylamino]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl}-5-methyl-benzonitrile

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A reaction mixture of 2-(4-chloro-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-5-methylbenzonitrile (160 mg, 0.56 mmol) and (S)-2-amino-2-(6-(trifluoromethyl)pyridin-3-yl)ethanol (118 mg, 0.57 mmol) (prepared similarly according to the method for Intermediate 10) in acetonitrile (2 mL) and N,N-diisopropylethylamine (0.4 mL) was subjected to microwave irradiation at 185° C. for 3.5 h. The reaction mixture was concentrated and the residue was purified by semi-preparative HPLC (100×20.2 mm, C18 column; 40-60% acetonitrile-water [10 mM diethylamine]) to yield a light brown solid.

Workup

  1. customprepared similarly
  2. customirradiation at 185° C. for 3.5 h
  3. concentrationThe reaction mixture was concentrated
  4. customthe residue was purified by semi-preparative HPLC (100×20.2 mm, C18 column; 40-60% acetonitrile-water [10 mM diethylamine])
  5. customto yield a light brown solid

Sources & evidence

ORD record
ord-aa6feee2e61c4d879dcce1f212a14a65
Source dataset
uspto-grants-2011_12
Patent number
US08076345B2

Reaction notes

Loading…