Diisopropylethylamine → tert-butyl 2-(4-fluorophenyl)-3-(4-((S)-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate

HRID 625057ノート

反応式

HRID 625057 の反応式
CCN(C(C)C)C(C)C.Cl.Cl.[CH3:12][C@H:13]1[C:21]2[C:20]([N:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)=[N:19][CH:18]=[N:17][C:16]=2[CH2:15][S:14]1.[C:28]([O:32][C:33]([N:35]([CH:48]([CH3:50])[CH3:49])[CH2:36][CH:37]([C:41]1[CH:46]=[CH:45][C:44]([F:47])=[CH:43][CH:42]=1)[C:38](O)=[O:39])=[O:34])([CH3:31])([CH3:30])[CH3:29].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>C(Cl)Cl.CCOC(C)=O>[F:47][C:44]1[CH:45]=[CH:46][C:41]([CH:37]([C:38]([N:25]2[CH2:26][CH2:27][N:22]([C:20]3[C:21]4[C@H:13]([CH3:12])[S:14][CH2:15][C:16]=4[N:17]=[CH:18][N:19]=3)[CH2:23][CH2:24]2)=[O:39])[CH2:36][N:35]([CH:48]([CH3:49])[CH3:50])[C:33](=[O:34])[O:32][C:28]([CH3:30])([CH3:29])[CH3:31])=[CH:42][CH:43]=1

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 674576973-(Tert-butoxycarbonyl(isopropyl)amino)-2-(4-fluorophenyl)propanoic acidHCID 67459940HCID 67459940、化合物

生成物 1

HCID 67459971tert-butyl 2-(4-fluorophenyl)-3-(4-((S)-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate収率 72%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

DIPEA (0.089 mL, 0.51 mmol) was added to a stirred suspension of (S)-5-methyl-4-(piperazin-1-yl)-5,7-dihydrothieno[3,4-d]pyrimidine dihydrochloride (40 mg, 0.13 mmol), 3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-fluorophenyl)propanoic acid (50 mg, 0.15 mmol) and O-(1H-Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (58 mg, 0.15 mmol) in DCM (10 mL) at room temperature. The reaction mixture was stirred at room temperature for 4 hours, diluted with EtOAc, washed with saturated aqueous bicarbonate and then 1N HCl. The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The residue was purified by silica gel chromatography (75% EtOAc/hexanes) to give tert-butyl 2-(4-fluorophenyl)-3-(4-((S)-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate (50 mg, 72% yield) as a mixture of 2 diastereomers. LCMS (APCI+) [M-Boc+H]+ 444.

後処理

  1. washwashed with saturated aqueous bicarbonate
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by silica gel chromatography (75% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-1a216a1c2438478ca1d7109c7cf0e986
出典データセット
uspto-grants-2016_04
特許番号
US09303040B2

反応ノート

読み込み中…