Borane;tetrahydrofuran → N-(3-chloro-4-fluorophenyl)-6-((methyl(2,2,2-trifluoroethyl)amino)methyl)-2-(pyridin-3-yl)quinazolin-4-amine

HRID 1520359Notes

Reaction equation

HRID 1520359 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([C:20]([N:22]([CH3:28])[CH2:23][C:24]([F:27])([F:26])[F:25])=O)[CH:18]=3)[N:13]=[C:12]([C:29]3[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=3)[N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].B.C1COCC1>CO>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([CH2:20][N:22]([CH3:28])[CH2:23][C:24]([F:27])([F:25])[F:26])[CH:18]=3)[N:13]=[C:12]([C:29]3[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=3)[N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

4

Reactant 2

HCID 2723981Borane;tetrahydrofuranHCID 67297980HCID 67297980, compound

Product 1

HCID 67298515N-(3-chloro-4-fluorophenyl)-6-((methyl(2,2,2-trifluoroethyl)amino)methyl)-2-(pyridin-3-yl)quinazolin-4-amineYield 26%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a mixture of 4-(3-chloro-4-fluorophenylamino)-N-methyl-2-(pyridin-3-yl)-N-(2,2,2-trifluoroethyl)quinazoline-6-carboxamide (60 mg, 0.12 mmol) THF (1 mL) was added BH3-THF (2 mol/L, 1 mL). The mixture was stirred at room temperature overnight. Methanol (0.2 mL) was added to quench the reaction mixture. The mixture was purified by prep-HPLC to give the desired product N-(3-chloro-4-fluorophenyl)-6-((methyl(2,2,2-trifluoroethyl)amino)methyl)-2-(pyridin-3-yl)quinazolin-4-amine (GL0001H-3309) as a white solid 15 mg in a yield of 26.0%. LCMS: r.t=2.154 min, [MH]+=476.1. 1H-NMR (400 MHz, DMSO-d6): δ 10.09 (s, 1H), 9.53 (s, 1H), 8.70-8.66 (m, 2H), 8.44 (s, 1H), 8.27-8.25 (m, 1H), 7.93-7.91 (m, 3H), 7.57-7.55 (m, 2H), 3.93 (s, 2H), 3.39-3.32 (m, 2H), 2.40 (s, 3H).

Workup

  1. customto quench the reaction mixture
  2. customThe mixture was purified by prep-HPLC

Sources & evidence

ORD record
ord-b60f005035384597b5d2fcf7d5ea248e
Source dataset
uspto-grants-2015_07
Patent number
US09073890B2

Reaction notes

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