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

HRID 511617
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HRID 511617 반응식
[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]3C[CH:13](C=O)[CH2:12]3)=[N:9][C:5]=2[CH:4]=1.[CH3:29][C:30]1([CH3:53])[O:34][C@@H:33]2[C@@H:35]([CH2:48][NH:49][CH:50]([CH3:52])[CH3:51])[CH2:36][C@@H:37]([N:38]3[C:42]4[N:43]=[CH:44][N:45]=[C:46]([NH2:47])[C:41]=4[CH:40]=[CH:39]3)[C@@H:32]2[O:31]1.[O-]S([O-])(=O)=O.[Mg+2].C([O-])(O)=O.[Na+]>ClCCCl.[Cl-].[Na+].O>[CH3:29][C:30]1([CH3:53])[O:34][C@@H:33]2[C@@H:35]([CH2:48][N:49]([CH:50]([CH3:51])[CH3:52])[CH2:13][CH2:12][CH2:11][CH2:10][C:8]3[N:7]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:23])([CH3:24])[CH3:22])[C:6]4[CH:25]=[CH:26][C:3]([C:2]([F:27])([F:1])[F:28])=[CH:4][C:5]=4[N:9]=3)[CH2:36][C@@H:37]([N:38]3[C:42]4[N:43]=[CH:44][N:45]=[C:46]([NH2:47])[C:41]=4[CH:40]=[CH:39]3)[C@@H:32]2[O:31]1
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반응물 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 866661163-{[5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]methyl}cyclobutane-1-carbaldehyde

생성물 1

HCID 86710537
7-[(3aS,4R,6R,6aR)-2,2-dimethyl-6-{[propan-2-yl({4-[5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]butyl})amino]methyl}-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine
수율 48.5%

시약·촉매·용매 2

HCID 111,2-Dichloroethane용매HCID 57417360Sodium chloride; water용매

실험 절차

A solution of 3-{[5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]methyl}cyclobutane-1-carbaldehyde (243 mg, 0.59 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 (170 mg, 0.49 mmol) and MgSO4 (710 mg, 5.90 mmol) in DCE (10 ml) was stirred for 15 min. STAB (175 mg, 0.83 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 1 h. Sat. NaHCO3 (20 ml) was added to the reaction mixture and stirred for 5 mins. Brine (10 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 silica gel column chromatography, eluting with 7N NH3 in MeOH:DCM (1:99-4:96) gave the desired product (170 mg, 47%) as an oil; MS (ESI+) for C38H54F3N7O3Si m/z 742.40 [M+H]+; HPLC purity 100% (ret. time, 1.78 min); 1H NMR (500 MHz, CHLOROFORM-d) δH ppm −0.25-0.11 (9H, m), 0.66-1.04 (8H, m), 1.17-1.48 (5H, m), 1.49-1.61 (3H, m), 1.77-2.04 (2H, m), 2.19-2.37 (5H, m), 2.37-2.51 (2H, m), 2.52-2.80 (2H, m), 2.81-2.91 (1H, m), 2.91-3.22 (2H, m), 3.34-3.79 (2H, m), 4.29-4.52 (1H, m), 4.78-5.12 (2H, m), 5.28-5.70 (4H, m), 6.34 (1H, d, J=3.63 Hz), 6.80-7.16 (1H, m), 7.29-7.71 (2H, m), 7.71-8.11 (1H, m), 8.11-8.46 (1H, m)

후처리

  1. additionSTAB (175 mg, 0.83 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 (1:99-4:96)

출처 및 근거

ORD 기록
ord-df8c5c85535d47c29be1dbd276327b70
출처 데이터셋
uspto-grants-2015_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09096634B2

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