Diisopropylethylamine → N1-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((2R,4R)-4-propoxypyrrolidin-2-yl)propan-2-yl)-N3,N3-dipropylisophthalamide

HRID 20956

反応式

HRID 20956 の反応式
[Si]([O:8][C@H:9]([C@H:32]1[CH2:36][C@@H:35]([O:37][CH2:38][CH2:39][CH3:40])[CH2:34][N:33]1C(OC(C)(C)C)=O)[C@@H:10]([NH:20][C:21](=[O:31])[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28](=[O:30])[NH2:29])[CH:23]=1)[CH2:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[C:14]([F:19])[CH:13]=1)(C(C)(C)C)(C)C.[CH2:48](O[C@H]1CN(C(C2C=CC=CC=2)C2C=CC=CC=2)[C@@H]([C@@H](O)[C@@H](NC(=O)C2C=CC=C(C(N(CCC)CCC)=O)C=2)CC2C=C(F)C=C(F)C=2)C1)[CH:49]=[CH2:50].[CH2:100](N(CCC)C(C1C=C(C=CC=1)C(O)=O)=O)[CH2:101][CH3:102].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(OC(N1C[C@H](OCCC)C[C@@H]1[C@@H](O[Si](C(C)(C)C)(C)C)[C@@H](NC(C1C=C(C=CC=1)C(O)=O)=O)CC1C=C(F)C=C(F)C=1)=O)(C)(C)C>ClCCl>[F:19][C:14]1[CH:13]=[C:12]([CH2:11][C@H:10]([NH:20][C:21](=[O:31])[C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([N:29]([CH2:100][CH2:101][CH3:102])[CH2:48][CH2:49][CH3:50])=[O:30])[CH:23]=2)[C@H:9]([OH:8])[C@H:32]2[CH2:36][C@@H:35]([O:37][CH2:38][CH2:39][CH3:40])[CH2:34][NH:33]2)[CH:17]=[C:16]([F:18])[CH:15]=1

参加物

8

反応物 6

HCID 81531DiisopropylethylamineHCID 1827693-(Dipropylcarbamoyl)benzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67315032(2R,4R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-2-(3-(carbamoyl)benzamido)-3-(3,5-difluorophenyl)propyl)-4-propoxypyrrolidine-1-carboxylateHCID 673161403-(((1S,2S)-1-((2R,4R)-1-(tert-butoxycarbonyl)-4-propoxypyrrolidin-2-yl)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propan-2-yl)carbamoyl)benzoic acidHCID 68497616N1-((1S,2S)-1-((2R,4R)-4-(allyloxy)-1-benzhydrylpyrrolidin-2-yl)-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl)-N3,N3-dipropylisophthalamide

生成物 1

HCID 11848526N1-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((2R,4R)-4-propoxypyrrolidin-2-yl)propan-2-yl)-N3,N3-dipropylisophthalamide収率 89%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

Step 4 (A): N1-((1S,2S)-1-((2R,4R)-4-(allyloxy)-1-benzhydrylpyrrolidin-2-yl)-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl)-N3,N3-dipropylisophthalamide. To a solution of 3-(dipropylcarbamoyl)benzoic acid (31 mg, 0.12 mmol) in dichloromethane (3 mL) were added Hunig's base (43 mg, 0.33 mmol) and HATU (54 mg, 0.143 mmol). After stirring for 20 min, the reaction mixture was added (1S,2S)-1-((2R,4R)-4-(allyloxy)-1-benzhydrylpyrrolidin-2-yl)-2-amino-3-(3,5-difluorophenyl)propan-1-ol (Preparation (C), 54 mg, 0.11 mmol) and the reaction mixture was stirred at rt overnight. The crude mixture was purified by silica gel Flash Chromatography (0% to 20% to 40% to 50% EtOAc/Hexane step gradient) to give 70 mg of the title compound (89% yield): 1H NMR (CDCl3, 500 MHz) δ 0.74 (3H, brd s), 1.00 (3H, brd s), 1.53 (2H, brd s), 1.73 (2H, brd s), 2.02-2.09 (1H, m), 2.17 (1H, d, J=10 Hz), 2.26 (1H, dd, J=5, 10 Hz), 2.68 (1H, d, J=10 Hz), 2.84 (1H, dd, J=5, 15 Hz), 2.96 (1H, dd, J=5, 15 Hz), 3.09 (1H, d, J=10 Hz), 3.16 (2H, brd s), 3.25 (1H, d, J=10 Hz), 3.49 (2H, brd s), 3.91-3.93 (2H, m), 3.96-4.11 (3H, m), 4.50 (1H, s), 4.91 (1H, d, J=10 Hz), 5.22 (1H, dd, J=5, 10 Hz), 5.31 (1H, m), 5.90-5.98 (1H, m), 6.64-6.69 (3H, m), 6.91-6.97 (3H, m), 7.15-7.20 (3H, m), 7.22-7.25 (2H, m), 7.34 (2H, d, J=5 Hz), 7.47-7.57 (4H, m). MS (ESI) (M+H)+ 710.37.

後処理

  1. stirringthe reaction mixture was stirred at rt overnight
  2. customThe crude mixture was purified by silica gel Flash Chromatography (0% to 20% to 40% to 50% EtOAc/Hexane step gradient)

出典と根拠

ORDレコード
ord-91d147b0b3cd45348f10ca34be92ec1f
出典データセット
uspto-grants-2010_06
特許番号
US07745470B2

関連ノート

読み込み中…