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

HRID 657803Notes

Reaction equation

HRID 657803 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:10]2[CH2:20][CH2:19][C:13]3[N:14]=[CH:15][N:16]=[C:17](Cl)[C:12]=3[CH2:11]2)=[C:6]([CH:9]=1)[C:7]#[N:8].[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>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:10]2[CH2:20][CH2:19][C:13]3[N:14]=[CH:15][N:16]=[C:17]([NH:21][C@@H:22]([C:25]4[CH:26]=[N:27][C:28]([C:31]([F:34])([F:32])[F:33])=[CH:29][CH:30]=4)[CH2:23][OH:24])[C:12]=3[CH2:11]2)=[C:6]([CH:9]=1)[C:7]#[N:8]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 58188187(S)-2-amino-2-(6-(trifluoromethyl)pyridin-3-yl)ethanolHCID 598406875-Chloro-2-(4-chloro-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)benzonitrile

Product 1

HCID 250595455-Chloro-2-{4-[(S)-2-hydroxy-1-(6-trifluoromethyl-pyridin-3-yl)-ethylamino]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl}-benzonitrileYield 18.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A reaction mixture of 5-chloro-2-(4-chloro-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)benzonitrile (150 mg, 0.49 mmol) and (S)-2-amino-2-(6-(trifluoromethyl)pyridin-3-yl)ethanol (150 mg, 0.74 mmol) (prepared similarly according to the method for Intermediate 10) in acetonitrile (3 mL) and N,N-diisopropylethylamine (170 μL, 0.98 mmol) was subjected to microwave irradiation at 180° C. for 4 h. The reaction mixture was concentrated and the residue was purified by silica gel column (100% EtOAc and then 0-20% MeOH/CH2Cl2) followed by semi-preparative HPLC (100×20.2 mm, C18 column; 30-70% acetonitrile-water [10 mM Et2NH]) to yield a light yellow foam (44 mg).

Workup

  1. customprepared similarly
  2. customirradiation at 180° C. for 4 h
  3. concentrationThe reaction mixture was concentrated
  4. customthe residue was purified by silica gel column (100% EtOAc

Sources & evidence

ORD record
ord-10d39d92154649ff8242dd5c380defb2
Source dataset
uspto-grants-2011_12
Patent number
US08076345B2

Reaction notes

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