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HOAt → N-(2-amino-4-(tert-butyl)phenyl)-3-(3-((((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(isopropyl)amino)cyclobutyl)propanamide

HRID 2040725
ノート
印刷プレビュー

反応式

HRID 2040725 の反応式
[CH3:1][O:2][C:3]1[CH:43]=[C:42]([O:44][CH3:45])[CH:41]=[CH:40][C:4]=1[CH2:5][NH:6][C:7]1[C:8]2[CH:15]=[CH:14][N:13]([C@H:16]3[C@@H:20]4[O:21][C:22]([CH3:25])([CH3:24])[O:23][C@@H:19]4[C@@H:18]([CH2:26][N:27]([CH:37]([CH3:39])[CH3:38])[CH:28]4[CH2:31][CH:30]([CH2:32][CH2:33][C:34](O)=[O:35])[CH2:29]4)[O:17]3)[C:9]=2[N:10]=[CH:11][N:12]=1.FC(F)(F)O[C:49]1[CH:50]=[C:51]([NH2:56])[C:52]([NH2:55])=[CH:53][CH:54]=1.CN(C(ON1N=NC2[CH:70]=[CH:71][CH:72]=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:83]1C=NC2N(O)N=NC=2C=1>C(Cl)Cl>[NH2:56][C:51]1[CH:50]=[C:49]([C:71]([CH3:70])([CH3:72])[CH3:83])[CH:54]=[CH:53][C:52]=1[NH:55][C:34](=[O:35])[CH2:33][CH2:32][CH:30]1[CH2:29][CH:28]([N:27]([CH2:26][C@@H:18]2[C@@H:19]3[C@@H:20]([O:21][C:22]([CH3:24])([CH3:25])[O:23]3)[C@H:16]([N:13]3[C:9]4[N:10]=[CH:11][N:12]=[C:7]([NH:6][CH2:5][C:4]5[CH:40]=[CH:41][C:42]([O:44][CH3:45])=[CH:43][C:3]=5[O:2][CH3:1])[C:8]=4[CH:15]=[CH:14]3)[O:17]2)[CH:37]([CH3:39])[CH3:38])[CH2:31]1
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 181649HOAtHCID 27739594-(Trifluoromethoxy)benzene-1,2-diamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 677769633-(3-((((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(isopropyl)amino)cyclobutyl)propanoic acid

生成物 1

HCID 67775308
N-(2-amino-4-(tert-butyl)phenyl)-3-(3-((((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(isopropyl)amino)cyclobutyl)propanamide
収率 67%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a solution of 3-(3-((((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(isopropyl)amino)cyclobutyl)propanoic acid (2.7 g, 4.33 mmol), 4-(trifluoromethoxy)benzene-1,2-diamine (1.23 g, 6.49 mmol), HATU (2.5 g, 6.49 mmol) and HOAT (0.88 g, 6.49 mmol) in DCM (30 mL) was added TEA (1.8 mL, 12.99 mmol). The mixture was stirred at rt for 2 h. The mixture was added DCM (70 mL) and washed with water (20 mL×2) and brine (50 mL). The organic phase was dried over Na2SO4, filtered and concentrated. The residue was purified by Combi-Flash (80 g silica gel, start EA:DCM:MeOH=10:10:0 to 10:10:2 by gradient, 60 mL/min, 40 min, 2.4 L total solvent volume) to afford to afford the desired compound (2.2 g, yield: 67% (two steps) as a brown solid. 1H NMR (500 MHz, MeOD): δH-8.21 (s, 1H), 7.28-7.12 (m, 3H), 6.73 (brs, 1H), 6.69 (brs, 1H), 6.56-6.52 (m, 2H), 6.42 (dd, J=8.0 and 2.5 Hz, 1H), 6.26 (d, J=1.5 Hz, 1H), 5.48 (d, J=6.0 Hz, 1H), 5.20-5.16 (m, 1H), 4.66 (s, 2H), 4.46-4.42 (m, 1H), 4.08-3.98 (m, 0.5H), 3.84 (s, 3H), 3.76 (s, 3H), 3.75-3.69 (m, 0.5H), 3.60-3.38 (m, 2H), 2.60-2.30 (m, 3H), 1.92-1.86 (m, 1H), 1.80-1.70 (m, 1H), 1.59 (d, J=3.5 Hz, 3H), 1.40 (s, 3H), 1.25 (t, J=7.5 Hz, 3H),), 1.00-0.80 (m, 2H) ppm; ESI-MS (m/z): 798.3 [M+1]+.

後処理

  1. washwashed with water (20 mL×2) and brine (50 mL)
  2. dry with materialThe organic phase was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by Combi-Flash (80 g silica gel, start EA:DCM:MeOH=10:10:0 to 10:10:2 by gradient, 60 mL/min, 40 min, 2.4 L total solvent volume)
  6. customto afford

出典と根拠

ORDレコード
ord-a78dce9799d14539903ee8d9dd31925b
出典データセット
uspto-grants-2013_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08580762B2

反応ノート

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