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

HRID 657810Notes

Reaction equation

HRID 657810 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:26]1[CH:27]=[N:28][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:30][CH:31]=1)[CH2:23][CH2:24][OH:25].C(N(CC)C(C)C)(C)C>C(#N)C>[OH:25][CH2:24][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:26]1[CH:27]=[N:28][C:29]([C:32]([F:33])([F:34])[F:35])=[CH:30][CH:31]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 58103584(R)-3-amino-3-(6-(trifluoromethyl)pyridin-3-yl)propan-1-olHCID 598406882-(4-Chloro-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-5-methylbenzonitrile

Product 1

HCID 598407022-{4-[(R)-3-Hydroxy-1-(6-trifluoromethyl-pyridin-3-yl)-propylamino]-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 (200 mg, 0.70 mmol) and (R)-3-amino-3-(6-(trifluoromethyl)pyridin-3-yl)propan-1-ol (180 mg, 0.82 mmol) in acetonitrile (2 mL) and N,N-diisopropylethylamine (0.7 mL, 4 mmol) was subjected to microwave irradiation at 185° C. for 2.5 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 Et2NH]) to yield an off-white solid.

Workup

  1. customirradiation at 185° C. for 2.5 h
  2. concentrationThe reaction mixture was concentrated
  3. customthe residue was purified by semi-preparative HPLC (100×20.2 mm, C18 column; 40-60% acetonitrile-water [10 mM Et2NH])
  4. customto yield an off-white solid

Sources & evidence

ORD record
ord-1d5d22e18016426dbcc103cf2f929834
Source dataset
uspto-grants-2011_12
Patent number
US08076345B2

Reaction notes

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