Diisopropylethylamine → (R)-N-(1-(3-cyclopropoxy-4-fluorophenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-methyl-5-(trifluoromethyl)oxazole-4-carboxamide

HRID 1874284ノート

反応式

HRID 1874284 の反応式
[CH:1]1([O:4][C:5]2[CH:6]=[C:7]([C@:12]([C:21]3[CH:26]=[C:25]([O:27][C:28]([F:33])([F:32])[CH:29]([F:31])[F:30])[CH:24]=[C:23]([F:34])[CH:22]=3)([NH2:20])[CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:8]=[CH:9][C:10]=2[F:11])[CH2:3][CH2:2]1.[CH3:35][C:36]1[O:37][C:38]([C:44]([F:47])([F:46])[F:45])=[C:39]([C:41](O)=[O:42])[N:40]=1.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH:1]1([O:4][C:5]2[CH:6]=[C:7]([C@@:12]([NH:20][C:41]([C:39]3[N:40]=[C:36]([CH3:35])[O:37][C:38]=3[C:44]([F:47])([F:45])[F:46])=[O:42])([C:21]3[CH:26]=[C:25]([O:27][C:28]([F:33])([F:32])[CH:29]([F:31])[F:30])[CH:24]=[C:23]([F:34])[CH:22]=3)[CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:8]=[CH:9][C:10]=2[F:11])[CH2:2][CH2:3]1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 27756512-methyl-5-(trifluoromethyl)-1,3-oxazole-4-carboxylic AcidHCID 59459264(R)-1-(3-cyclopropoxy-4-fluorophenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethanamine

生成物 1

HCID 59459256(R)-N-(1-(3-cyclopropoxy-4-fluorophenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-methyl-5-(trifluoromethyl)oxazole-4-carboxamide収率 70%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of (R)-1-(3-cyclopropoxy-4-fluorophenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethanamine, prepared as described in Procedure 109, 110, 111, 112, 113, 114, 161, (24 mg, 0.05 mmol) in CH2Cl2 (0.5 mL) was added 2-methyl-5-(trifluoromethyl)-oxazole-4-carboxylic acid (12 mg, 0.06 mmol), followed by PyBrOP (28 mg, 0.06 mmol) and iPr2NEt (9 mg, 0.065 mmol). The reaction mixture was stirred at rt for 72 h. The reaction mixture was concentrated under reduced pressure and the residue was purified by prep HPLC (Phenomenex Luna 5μ 30×100 mm, eluting with 10%-90% MeOH/H2O containing 0.1% TFA, gradient time 10 min, flow rate 40 mL/min) to yield (R)—N-(1-(3-cyclopropoxy-4-fluorophenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-methyl-5-(trifluoromethyl)oxazole-4-carboxamide (Example 347) as a white solid (23 mg, 70% yield). HPLC: RT=2.18 min [M+H] 659.5 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm); 1H NMR (400 MHz, CDCl3) δ ppm 7.79, s, 1H, 7.10-7.20, m, 3H, 6.90-7.03, m, 5H, 6.70, s, 1H, 6.68, s, 1H, 6.55-6.58, m, 1H, 5.74-6.00, t, J=52; 4.15, 4.19, d, J=16, 1H, 3.66-3.69, d, J=12, 1H, 3.51-3.54, m, 1H, 0.73-0.80, m, 1H, 0.61-0.69, m, 2H, 0.55-0.60, m, 1H.

後処理

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe residue was purified by prep HPLC (Phenomenex Luna 5μ 30×100 mm, eluting with 10%-90% MeOH/H2O containing 0.1% TFA, gradient time 10 min, flow rate 40 mL/min)

出典と根拠

ORDレコード
ord-69c14edfb90f4c57adf950e03fa985e3
出典データセット
uspto-grants-2012_11
特許番号
US08304403B2

反応ノート

読み込み中…