Sulfuric acid magnesium salt (1:1) → HCID 67816584, compound

HRID 1054541Notes

Reaction equation

HRID 1054541 reaction equation
[O-]S([O-])(=O)=O.[Mg+2].[Cl:7][C:8]1[C:9]([C:30]([F:33])([F:32])[F:31])=[CH:10][C:11]2[N:15]=[C:14]([CH2:16][CH2:17][CH2:18][CH:19]=O)[N:13]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:12]=2[CH:29]=1.[CH3:34][C:35]1([CH3:61])[O:39][C@@H:38]2[C@@H:40]([CH2:56][NH:57][CH:58]([CH3:60])[CH3:59])[CH2:41][C@@H:42]([N:43]3[C:47]4[N:48]=[CH:49][N:50]=[C:51]([NH:52][CH:53]5[CH2:55][CH2:54]5)[C:46]=4[CH:45]=[CH:44]3)[C@@H:37]2[O:36]1.C([O-])(O)=O.[Na+]>ClCCCl.[Cl-].[Na+].O>[Cl:7][C:8]1[C:9]([C:30]([F:33])([F:31])[F:32])=[CH:10][C:11]2[N:15]=[C:14]([CH2:16][CH2:17][CH2:18][CH2:19][N:57]([CH2:56][C@@H:40]3[C@H:38]4[O:39][C:35]([CH3:61])([CH3:34])[O:36][C@H:37]4[C@H:42]([N:43]4[C:47]5[N:48]=[CH:49][N:50]=[C:51]([NH:52][CH:53]6[CH2:55][CH2:54]6)[C:46]=5[CH:45]=[CH:44]4)[CH2:41]3)[CH:58]([CH3:59])[CH3:60])[N:13]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:27])([CH3:26])[CH3:28])[C:12]=2[CH:29]=1

Participants

7

Reactant 4

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 516892Sodium BicarbonateHCID 67817502HCID 67817502, compoundHCID 86705755HCID 86705755, compound

Product 1

HCID 67816584HCID 67816584, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

MgSO4 (450 mg, 3.74 mmol) was added to a solution of 4-[6-chloro-5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]butanal (189 mg, 0.45 mmol) and 7-[(3aS,4R,6R,6aR)-2,2-dimethyl-6-[(propan-2-ylamino)methyl]-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-N-cyclopropyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (145 mg, 0.37 mmol) in DCE (10 ml) at RT and stirred for 15 mins. Na(AcO)3BH (111 mg, 0.52 mmol) was then added and continued stirring at RT for 2 hours. Sat. NaHCO3 (30 ml) was added to the reaction mixture and stirred for 5 mins. Brine (10 ml) was added to the reaction mixture, the organic layer was separated and the aqueous was further extracted with DCM (30 ml). The combined organic layers was dried over Na2SO4, filtered and evaporated. The crude mixture was dissolved in MeCN:H2O (8:2) (4 ml) and purified by preparative HPLC under acidic conditions to give a colourless oil (105 mg, 42%); MS (ESI+) for C39H55ClF3N7O3Si m/z 790.35 [M+H]+: HPLC purity 90% (ret. time, 1.90 min): 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 10.98 (1H, br. s.), 8.07 (6.98-7.10 (1H, m), 1H, d, J=1.89 Hz), 7.87-8.01 (1H, m), 7.70 (1H, s), 7.16-7.25 (1H, m), 5.50-5.69 (2H, m), 4.96 (2H, br. s.), 4.66 (1H, br. s.), 4.28-4.39 (1H, m), 3.82 (1H, br. s.), 3.55-3.69 (2H, m), 3.15-3.33 (5H, m), 3.05-3.14 (1H, m), 2.94-3.03 (1H, m), 2.49-2.83 (2H, m), 2.23-2.49 (1H, m), 1.83-2.16 (4H, m), 1.53 (3H, d, J=11.51 Hz), 1.33-1.46 (6H, m), 1.28 (3H, d, J=7.72 Hz), 0.99-1.10 (2H, m), 0.94 (4H, dd, J=3.39, 1.18 Hz), −0.26-0.15 (9H, m)

Workup

  1. stirringcontinued stirring at RT for 2 hours
  2. stirringstirred for 5 mins
  3. customthe organic layer was separated
  4. extractionthe aqueous was further extracted with DCM (30 ml)
  5. dry with materialThe combined organic layers was dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. dissolutionThe crude mixture was dissolved in MeCN:H2O (8:2) (4 ml)
  9. custompurified by preparative HPLC under acidic conditions

Sources & evidence

ORD record
ord-0e20ddaefa2440a1a0a7f53c94960efe
Source dataset
uspto-grants-2016_07
Patent number
US09394310B2

Reaction notes

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