Ethylamine hydrochloride → 2-(4-{3-[2-Chloro-4-(2,4-difluoro-phenylamino)-benzoyl]-4-methyl-phenyl}-[1,2,3]triazol-1-yl)-N-ethyl-acetamide

HRID 2067206Notes

Reaction equation

HRID 2067206 reaction equation
[Cl:1][C:2]1[CH:25]=[C:24]([NH:26][C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][C:28]=2[F:34])[CH:23]=[CH:22][C:3]=1[C:4]([C:6]1[CH:7]=[C:8]([C:13]2[N:14]=[N:15][N:16]([CH2:18][C:19](O)=[O:20])[CH:17]=2)[CH:9]=[CH:10][C:11]=1[CH3:12])=[O:5].Cl.[CH2:36]([NH2:38])[CH3:37].C1C=CC(P(OC2C(F)=C(F)C(F)=C(F)C=2F)(C2C=CC=CC=2)=O)=CC=1.CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:1][C:2]1[CH:25]=[C:24]([NH:26][C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][C:28]=2[F:34])[CH:23]=[CH:22][C:3]=1[C:4]([C:6]1[CH:7]=[C:8]([C:13]2[N:14]=[N:15][N:16]([CH2:18][C:19]([NH:38][CH2:36][CH3:37])=[O:20])[CH:17]=2)[CH:9]=[CH:10][C:11]=1[CH3:12])=[O:5]

Participants

6

Reactant 4

HCID 11198Ethylamine hydrochlorideHCID 81531DiisopropylethylamineHCID 4652311Pentafluorophenyl diphenylphosphinateHCID 11496723(4-{3-[2-Chloro-4-(2,4-difluoro-phenylamino)-benzoyl]-4-methyl-phenyl}-[1,2,3]triazol-1-yl)-acetic acid

Product 1

HCID 115986752-(4-{3-[2-Chloro-4-(2,4-difluoro-phenylamino)-benzoyl]-4-methyl-phenyl}-[1,2,3]triazol-1-yl)-N-ethyl-acetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of compound 111 (39 mg, 0.08 mmol) in DMF (1.0 mL) was added ethylamine hydrochloride (20 mg, 0.08 mmol), FDPP (43 mg, 0.11 mmol), and DIEA (68 μL, 0.4 mmol). The flask was flushed with argon and the reaction mixture was stirred at RT for 72 h and then poured into a mixture of water (4 mL), HCl (4N, 2 mL), and EtOAc. The phases were separated. The organic phase was concentrated on silica in vacuo. The crude product was purified by chromatography eluting with EtOAc/petroleum ether (40-60) 50:50 to 100:0 as the eluent to afford the title compound as white foam. 13C NMR (DMSO-d6) δ 194.9, 164.8, 149.3, 145.2, 139.8, 135.9, 133.7, 133.7, 131.7, 128.2, 127.1, 126.6, 126.4 (dd), 125.0, 124.2 (dd), 123.0, 114.8, 111.9 (dd), 111.8, 105.0 (dd), 51.7, 33.6, 19.4, 14.4

Workup

  1. customThe flask was flushed with argon
  2. additionpoured into a mixture of water (4 mL), HCl (4N, 2 mL), and EtOAc
  3. customThe phases were separated
  4. concentrationThe organic phase was concentrated on silica in vacuo
  5. customThe crude product was purified by chromatography
  6. washeluting with EtOAc/petroleum ether (40-60) 50:50 to 100:0 as the eluent

Sources & evidence

ORD record
ord-db3efbe32a514f558cf7b6ec85206638
Source dataset
uspto-grants-2012_10
Patent number
US08293772B2

Reaction notes

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