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

HRID 2040669ノート

反応式

HRID 2040669 の反応式
[Cl:1][C:2]1[C:3]([C:26]([F:29])([F:28])[F:27])=[CH:4][C:5]2[N:9]=[C:8]([CH2:10][CH:11]3[CH2:14][CH:13]([CH:15]=O)[CH2:12]3)[N:7]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:6]=2[CH:25]=1.[CH3:30][C:31]1([CH3:54])[O:35][C@@H:34]2[C@@H:36]([CH2:49][NH:50][CH:51]([CH3:53])[CH3:52])[CH2:37][C@@H:38]([N:39]3[C:43]4[N:44]=[CH:45][N:46]=[C:47]([NH2:48])[C:42]=4[CH:41]=[CH:40]3)[C@@H:33]2[O:32]1.[O-]S([O-])(=O)=O.[Mg+2].C([O-])(O)=O.[Na+]>ClCCCl.[Cl-].[Na+].O>[Cl:1][C:2]1[C:3]([C:26]([F:29])([F:27])[F:28])=[CH:4][C:5]2[N:9]=[C:8]([CH2:10][CH:11]3[CH2:12][CH:13]([CH2:15][N:50]([CH2:49][C@@H:36]4[C@H:34]5[O:35][C:31]([CH3:54])([CH3:30])[O:32][C@H:33]5[C@H:38]([N:39]5[C:43]6[N:44]=[CH:45][N:46]=[C:47]([NH2:48])[C:42]=6[CH:41]=[CH:40]5)[CH2:37]4)[CH:51]([CH3:52])[CH3:53])[CH2:14]3)[N:7]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:22])[CH3:23])[C:6]=2[CH:25]=1

参加物

7

反応物 4

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 516892Sodium BicarbonateHCID 677763337-[(3aS,4R,6R,6aR)-2,2-dimethyl-6-[(propan-2-ylamino)methyl]-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amineHCID 866661203-{[6-chloro-5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]methyl}cyclobutane-1-carbaldehyde

生成物 1

HCID 677763577-[(3aS,4R,6R,6aR)-6-({[(3-{[6-chloro-5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]methyl}cyclobutyl)methyl](propan-2-yl)amino]methyl)-2,2-dimethyl-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine収率 45%

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 57417360Sodium chloride; water溶媒

実験手順

A solution of 3-{[6-chloro-5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]methyl}cyclobutane-1-carbaldehyde (223 mg, 0.50 mmol), 7-[(3aS,4R,6R,6aR)-2,2-dimethyl-6-[(propan-2-ylamino)methyl]-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine (172 mg, 0.50 mmol) and MgSO4 (600 mg, 5.00 mmol) in DCE (10 ml) was stirred for 15 min. STAB (148 mg, 0.70 mmol) was then added to the reaction mixture and stirred for 1 h at RT. The reaction was monitored by LCMS, no amine was seen after 2.5 h. Sat. NaHCO3 (20 ml) was added to the reaction mixture and stirred for 5 mins Brine (20 ml) was then added to the reaction mixture. The product was extracted with DCM (2×30 ml), dried over Na2SO4, filtered and evaporated. Purification by prep. HPLC gave the desired product (174 mg, 45%) as a white solid; MS (EST) for C38H53ClF3N7O3Si m/z 776.30 [M+H]+; HPLC purity 100% (ret. time, 1.68 min); 1H NMR (500 MHz, MeOD) δH ppm −0.25-0.11 (9 H, m), 0.90 (2 H, td, J=7.88, 3.47 Hz), 1.30 (3 H, s), 1.37 (6 H, t, J=7.49 Hz), 1.55 (3 H, s), 1.63-1.84 (1 H, m), 1.99-2.37 (2 H, m), 2.37-3.03 (6 H, m), 3.04-3.28 (3 H, m), 3.34-3.50 (1 H, m), 3.61 (2 H, td, J=7.92, 2.29 Hz), 3.79 (1 H, br. s.), 4.68 (1 H, t, J=6.70 Hz), 4.95-5.27 (2 H, m), 5.55-5.81 (1 H, m), 6.88 (1 H, d, j=3.63 Hz), 7.06-7.62 (2 H, m), 7.61-7.94 (1 H, m), 7.94-8.16 (1 H, m), 8.22 (1 H, s)

後処理

  1. additionSTAB (148 mg, 0.70 mmol) was then added to the reaction mixture
  2. additionwas then added to the reaction mixture
  3. extractionThe product was extracted with DCM (2×30 ml)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customPurification by prep

出典と根拠

ORDレコード
ord-ccbd1571115f48529d788aa4cbe7efff
出典データセット
uspto-grants-2013_11
特許番号
US08580762B2

反応ノート

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