1,2-Dichloroethane → 2',4'-Difluoro-5-piperazin-1-yl-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}biphenyl-3-carboxamide

HRID 888389ノート

反応式

HRID 888389 の反応式
C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[C:16]([C:28]([OH:30])=O)[CH:17]=[C:18]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=3[F:27])[CH:19]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.Cl.[F:33][C:34]([F:45])([F:44])[C:35]1[N:40]=[CH:39][C:38]([C@H:41]([NH2:43])[CH3:42])=[CH:37][N:36]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.Cl>CN(C)C=O>[F:27][C:21]1[CH:22]=[C:23]([F:26])[CH:24]=[CH:25][C:20]=1[C:18]1[CH:19]=[C:14]([N:11]2[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]2)[CH:15]=[C:16]([C:28]([NH:43][C@@H:41]([C:38]2[CH:37]=[N:36][C:35]([C:34]([F:45])([F:44])[F:33])=[N:40][CH:39]=2)[CH3:42])=[O:30])[CH:17]=1

参加物

8

反応物 6

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 66690185(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethanamine dihydrochlorideHCID 684965535-[4-(Tert-butoxycarbonyl)piperazin-1-yl]-2',4'-difluorobiphenyl-3-carboxylic acid

生成物 1

HCID 426029932',4'-Difluoro-5-piperazin-1-yl-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}biphenyl-3-carboxamide収率 80.3%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 5-[4-(tert-butoxycarbonyl)piperazin-1-yl]-2′,4′-difluorobiphenyl-3-carboxylic acid (30.0 mg, 0.072 mmol), in N,N-dimethylformamide (1.0 mL) was added (1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethanamine dihydrochloride (22.7 mg, 0.086 mmol), EDC (17.8 mg, 0.093 mmol), HOBT (11.0 mg, 0.072 mmol) and diisopropylethylamine (0.038 mL, 0.215 mmol). After 16 h, the mixture was acidified with hydrochloric acid gas. After 15 min, the mixture was concentrated and purified by reverse phase HPLC (C-18, 95% water/acetonitrile→25% water/acetonitrile with 0.1% trifluoroacetic acid) to give the title compound (28.4 mg). HRMS 492.1833 (M+1). 1H NMR (500 MHz, CD3OD): δ 9.00 (s, 2H); 7.57-7.50 (m, 1H); 7.47-7.43 (m, 2H); 7.24 (q, J=1.7 Hz, 1H); 7.09-7.03 (m, 2H); 5.33 (q, J=7.1 Hz, 1H); 3.25 (t, J=4.9 Hz, 4H); 3.00 (t, J=4.7 Hz, 4H); 1.68 (d, J=7.2 Hz, 3H).

後処理

  1. waitAfter 15 min
  2. concentrationthe mixture was concentrated
  3. custompurified by reverse phase HPLC (C-18, 95% water/acetonitrile→25% water/acetonitrile with 0.1% trifluoroacetic acid)

出典と根拠

ORDレコード
ord-6ee96bed8d394fe88d76d173f770c92a
出典データセット
uspto-grants-2012_08
特許番号
US08247401B2

反応ノート

読み込み中…