1,2-Dichloroethane → 7-[(3aS,4R,6R,6aR)-2,2-dimethyl-6-(({(3-{[5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]methyl}cyclobutyl)methyl]amino}methyl)-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine

HRID 511621ノート

反応式

HRID 511621 の反応式
[F:1][C:2]([F:28])([F:27])[C:3]1[CH:26]=[CH:25][C:6]2[N:7]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:8]([CH2:10][CH:11]3[CH2:14][CH:13]([CH:15]=O)[CH2:12]3)=[N:9][C:5]=2[CH:4]=1.[NH2:29][C:30]1[C:31]2[CH:38]=[CH:37][N:36]([C@@H:39]3[CH2:43][C@H:42]([CH2:44][NH2:45])[C@@H:41]([OH:46])[C@H:40]3[OH:47])[C:32]=2[N:33]=[CH:34][N:35]=1.[O-]S([O-])(=O)=O.[Mg+2].[C:54]([O-])(O)=O.[Na+].Cl[CH2:60][CH2:61]Cl>[Cl-].[Na+].O>[CH3:54][C:60]1([CH3:61])[O:46][C@@H:41]2[C@@H:42]([CH2:44][NH:45][CH2:15][CH:13]3[CH2:14][CH:11]([CH2:10][C:8]4[N:7]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:22])([CH3:23])[CH3:24])[C:6]5[CH:25]=[CH:26][C:3]([C:2]([F:28])([F:1])[F:27])=[CH:4][C:5]=5[N:9]=4)[CH2:12]3)[CH2:43][C@@H:39]([N:36]3[C:32]4[N:33]=[CH:34][N:35]=[C:30]([NH2:29])[C:31]=4[CH:38]=[CH:37]3)[C@@H:40]2[O:47]1

参加物

7

反応物 5

HCID 111,2-DichloroethaneHCID 24083Sulfuric acid magnesium salt (1:1)HCID 516892Sodium BicarbonateHCID 67776418(1R,2S,3R,5R)-3-{4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-5-(aminomethyl)cyclopentane-1,2-diolHCID 866661163-{[5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]methyl}cyclobutane-1-carbaldehyde

生成物 1

HCID 677756727-[(3aS,4R,6R,6aR)-2,2-dimethyl-6-(({(3-{[5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]methyl}cyclobutyl)methyl]amino}methyl)-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine

試薬・触媒・溶媒 1

HCID 57417360Sodium chloride; water溶媒

実験手順

A solution of 3-{[5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]methyl}cyclobutane-1-carbaldehyde (190 mg, 0.46 mmol), (1R,2S,3R,5R)-3-{4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-5-(aminomethyl)cyclopentane-1,2-diol (140 mg, 0.46 mmol) and MgSO4 (554 mg, 4.61 mmol) in DCE (10 ml) was stirred for 15 min. STAB (137 mg, 0.645 mmol) was then added to the reaction mixture and stirred. The reaction was monitored by LCMS, after which no amine was seen. Sat. NaHCO3 (20 ml) was added to the reaction mixture and stirred for 5 mins. Brine (10 ml) was added to the reaction mixture and the product was extracted with DCM (2×30 ml), dried over Na2SO4, filtered and evaporated. Purification by silica gel column chromatography, eluting with 7N NH3 in MeOH:DCM (1:99-5:95) gave the desired product as a pink foamy solid. The mixed fractions were combined and purified on a prep. TLC plate eluting with 7N NH3 in MeOH:DCM (2×4:96) to give a total of 170 mg, 53%. MS (ESI+) for C35H48F3N7O3Si m/z 700 [M+H]+; HPLC purirty 100% (ret. time, 1.79 min); 1H NMR (250 MHz, CHLOROFORM-d) δH ppm −0.26-0.16 (9H, m), 0.72-0.97 (2H, m), 1.30 (3H, s), 1.38-1.60 (5H, m), 1.91-2.59 (8H, 2.60-3.27 (6H, m), 3.35-3.70 (2H, m), 4.52 (1H, t, J=5.94 Hz), 4.78-5.20 (4H, m), 5.39-5.66 (2H, m), 6.36 (1H, d, J=3.65 Hz), 7.03 (1H, d, J=3.65 Hz), 7.42-7.59 (1H, m), 7.69 (1H, s), 7.79 (1H, d, J=8.53 Hz), 8.32 (1H, s).

後処理

  1. additionSTAB (137 mg, 0.645 mmol) was then added to the reaction mixture
  2. stirringstirred for 5 mins
  3. extractionthe product was extracted with DCM (2×30 ml)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customPurification by silica gel column chromatography
  8. washeluting with 7N NH3 in MeOH:DCM (1:99-5:95)

出典と根拠

ORDレコード
ord-7cf1b038a2e8486db9f28710008a96d1
出典データセット
uspto-grants-2015_08
特許番号
US09096634B2

反応ノート

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