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 2040669Notes

Reaction equation

HRID 2040669 reaction equation
[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

Participants

7

Reactant 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

Product 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-amineYield 45%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

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)

Workup

  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

Sources & evidence

ORD record
ord-ccbd1571115f48529d788aa4cbe7efff
Source dataset
uspto-grants-2013_11
Patent number
US08580762B2

Reaction notes

Loading…