Trifluoroacetic acid → 4-Amino-2-(4-((2-chloro-8-(4-fluorophenyl)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)amino)butoxy)benzonitrile

HRID 474276Notes

Reaction equation

HRID 474276 reaction equation
[NH2:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:10][CH2:11][CH2:12][CH2:13][CH2:14][NH2:15])[CH:3]=1.C(O)(C(F)(F)F)=O.[Cl:23][C:24]1[N:25]=[C:26](Cl)[C:27]2[CH2:33][N:32]([CH3:34])[CH2:31][CH:30]([C:35]3[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=3)[C:28]=2[N:29]=1.CCN(C(C)C)C(C)C>C(#N)C>[NH2:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:10][CH2:11][CH2:12][CH2:13][CH2:14][NH:15][C:26]2[C:27]3[CH2:33][N:32]([CH3:34])[CH2:31][CH:30]([C:35]4[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=4)[C:28]=3[N:29]=[C:24]([Cl:23])[N:25]=2)[CH:3]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 580753632,4-Dichloro-8-(4-fluorophenyl)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-D]pyrimidineHCID 666656284-Amino-2-(4-aminobutoxy)benzonitrile

Product 1

HCID 866681194-Amino-2-(4-((2-chloro-8-(4-fluorophenyl)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)amino)butoxy)benzonitrileYield 15.72%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 4-amino-2-(4-aminobutoxy)benzonitrile, 2 TFA salt (Preparation X, 23.32 mg, 0.054 mmol), 2,4-dichloro-8-(4-fluorophenyl)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (Preparation V, 14 mg, 0.045 mmol) and DIEA (39.2 μL, 0.224 mmol) in acetonitrile (224 μL) was stirred at rt for 4 h. The crude product was purified by Prep-HPLC to obtain 4-amino-2-(4-((2-chloro-8-(4-fluorophenyl)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)amino)butoxy)benzonitrile, (5.0 mg, 15.72% yield). LC-MS (M+Na)+=481.2. 1H NMR (500 MHz, methanol-d4) δ 7.26-7.18 (m, 3H), 7.16-7.08 (m, 2H), 6.33 (d, J=2.0 Hz, 1H), 6.28 (dd, J=8.5, 1.9 Hz, 1H), 4.45 (dd, J=10.5, 6.3 Hz, 1H), 4.30 (d, J=11.6 Hz, 2H), 4.10 (t, J=5.6 Hz, 2H), 3.89 (dd, J=12.4, 6.3 Hz, 1H), 3.70-3.52 (m, 3H), 3.18-3.08 (m, 3H), 2.01-1.80 (m, 4H).

Workup

  1. customThe crude product was purified by Prep-HPLC

Sources & evidence

ORD record
ord-bf5c7c65d2964fde9ce37707fc4665f0
Source dataset
uspto-grants-2014_01
Patent number
US08637523B2

Reaction notes

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