Trifluoroacetic acid → Trifluoroacetic acid

HRID 474275Notes

Reaction equation

HRID 474275 reaction equation
[CH3:1][C:2]1[N:6]=[CH:5][N:4]([C:7]2[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][C:8]=2[O:9][CH2:10][CH2:11][CH2:12][CH2:13][NH2:14])[N:3]=1.[C:22]([OH:28])([C:24]([F:27])([F:26])[F:25])=[O:23].[Cl:29][C:30]1[N:31]=[C:32](Cl)[C:33]2[CH2:39][N:38]([CH3:40])[CH2:37][CH:36]([C:41]3[CH:46]=[CH:45][C:44]([F:47])=[CH:43][CH:42]=3)[C:34]=2[N:35]=1.CCN(C(C)C)C(C)C>C(#N)C.CO>[Cl:29][C:30]1[N:31]=[C:32]([NH:14][CH2:13][CH2:12][CH2:11][CH2:10][O:9][C:8]2[CH:15]=[C:16]([N+:19]([O-:21])=[O:20])[CH:17]=[CH:18][C:7]=2[N:4]2[CH:5]=[N:6][C:2]([CH3:1])=[N:3]2)[C:33]2[CH2:39][N:38]([CH3:40])[CH2:37][CH:36]([C:41]3[CH:46]=[CH:45][C:44]([F:47])=[CH:43][CH:42]=3)[C:34]=2[N:35]=1.[C:22]([OH:28])([C:24]([F:27])([F:26])[F:25])=[O:23]

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 580753632,4-Dichloro-8-(4-fluorophenyl)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-D]pyrimidineHCID 666659904-(2-(3-methyl-1H-1,2,4-triazol-1-yl)-5-nitrophenoxy)butan-1-amine

Product 2

HCID 6422Trifluoroacetic acidYield 82%HCID 866681182-chloro-8-(4-fluorophenyl)-6-methyl-N-(4-(2-(3-methyl-1H-1,2,4-triazol-1-yl)-5-nitrophenoxy)butyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-amine

Reagents, catalysts & solvents 2

HCID 887MethanolCatalystHCID 6342AcetonitrileSolvent

Procedure

The mixture of 4-(2-(3-methyl-1H-1,2,4-triazol-1-yl)-5-nitrophenoxy)butan-1-amine, 2 TFA (46.6 mg, 0.090 mmol), 2,4-dichloro-8-(4-fluorophenyl)-6-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (20 mg, 0.064 mmol) and DIEA (55.9 μL, 0.320 mmol) in acetonitrile (320 μL) and 2 drops of MeOH was stirred at rt overnight. The crude product was purified by Prep-HPLC to obtain 2-chloro-8-(4-fluorophenyl)-6-methyl-N-(4-(2-(3-methyl-1H-1,2,4-triazol-1-yl)-5-nitrophenoxy)butyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-amine, 2 TFA (43.6 mg, 82% yield). LC-MS (M+H)+=567.2. 1H NMR (500 MHz, methanol-d4) δ 9.00 (s, 1H), 8.06 (d, J=2.1 Hz, 1H), 8.03-7.95 (m, 2H), 7.21-7.12 (m, 2H), 7.04-6.96 (m, 2H), 4.39 (t, J=6.3 Hz, 2H), 4.00 (s, 1H), 3.60-3.52 (m, 2H), 3.42-3.23 (m, 2H), 2.94 (dd, J=11.7, 5.4 Hz, 1H), 2.68 (dd, J=11.7, 6.0 Hz, 1H), 2.48-2.39 (m, 6H), 1.99 (t, J=6.8 Hz, 2H), 1.84 (td, J=7.2, 3.4 Hz, 2H).

Workup

  1. customThe crude product was purified by Prep-HPLC

Sources & evidence

ORD record
ord-9739b53c639f4b279bd34bbc482720a4
Source dataset
uspto-grants-2014_01
Patent number
US08637523B2

Reaction notes

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