Sulfuric acid magnesium salt (1:1) → HCID 86705758, compound

HRID 1054543Notes

Reaction equation

HRID 1054543 reaction equation
[Cl:1][C:2]1[C:3]([C:24]([F:27])([F:26])[F:25])=[CH:4][C:5]2[N:9]=[C:8]([CH2:10][CH2:11][CH2:12][CH:13]=O)[N:7]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[C:6]=2[CH:23]=1.[NH2:28][CH2:29][C@@H:30]1[C@H:34]2[O:35][C:36]([CH3:39])([CH3:38])[O:37][C@H:33]2[C@H:32]([N:40]2[C:44]3[N:45]=[CH:46][N:47]=[C:48]([NH:49][CH:50]4[CH2:52][CH2:51]4)[C:43]=3[CH:42]=[CH:41]2)[CH2:31]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:24]([F:27])([F:25])[F:26])=[CH:4][C:5]2[N:9]=[C:8]([CH2:10][CH2:11][CH2:12][CH2:13][NH:28][CH2:29][C@@H:30]3[C@H:34]4[O:35][C:36]([CH3:38])([CH3:39])[O:37][C@H:33]4[C@H:32]([N:40]4[C:44]5[N:45]=[CH:46][N:47]=[C:48]([NH:49][CH:50]6[CH2:52][CH2:51]6)[C:43]=5[CH:42]=[CH:41]4)[CH2:31]3)[N:7]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:21])([CH3:20])[CH3:22])[C:6]=2[CH:23]=1

Participants

7

Reactant 4

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 516892Sodium BicarbonateHCID 67816524HCID 67816524, compoundHCID 86705755HCID 86705755, compound

Product 1

HCID 86705758HCID 86705758, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of the 4-[6-chloro-5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]butanal (367 mg, 0.87 mmol), 7-[(3aS,4R,6R,6aR)-6-(aminomethyl)-2,2-dimethyl-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-N-cyclopropyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (300 mg, 0.87 mmol) and MgSO4 (1.05 g, 8.74 mmol) in DCE (10 ml) was stirred at RT for 15 min. Na(AcO)3BH (259 mg, 1.22 mmol) was then added to the reaction mixture and stirred for 1 hour. 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), the combined extracts were dried over Na2SO4, filtered and concentrated. Purification by silica gel column chromatography, eluting with 7N NH3 in MeOH:DCM (1:199-3:97) gave the desired product as a pink foamy solid. The mixed fractions were combined and purified on a preparative TLC plate eluting with 7N NH3 in MeOH:DCM (2×4:96) to give an off white solid (270 mg, 41%): MS (ESI+) for C36H49ClF3N7O3Si m/z 748.25 [M+H]+; HPLC purity>95% (ret. time, 1.75 min); 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 8.14-8.47 (1H, m), 7.78-8.11 (1H, m), 7.40-7.78 (1H, m), 6.99 (1H, d, J=3.63 Hz), 6.63 (1H, br. s.), 5.34-5.69 (3H, m), 4.81-5.11 (2H, m), 4.53 (1H, t, J=6.15 Hz), 3.33-3.71 (2H, m), 2.89-3.14 (3H, m), 2.77-2.90 (1H, m), 2.68-2.79 (3H, m), 2.25-2.49 (2H, m), 2.15 (1H, q, J=11.87 Hz), 1.89-2.06 (2H, m), 1.63-1.71 (2H, m), 1.51-1.61 (3H, m), 1.21-1.37 (3H, m), 0.84-1.00 (4H, m), 0.62-0.78 (2H, m), −0.15-0.06 (9H, m).

Workup

  1. stirringstirred for 5 mins
  2. extractionthe product was extracted with DCM (2×30 ml)
  3. dry with materialthe combined extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by silica gel column chromatography
  7. washeluting with 7N NH3 in MeOH:DCM (1:199-3:97)

Sources & evidence

ORD record
ord-ac9b66712e5c4f4c9838add6a0b48f06
Source dataset
uspto-grants-2016_07
Patent number
US09394310B2

Reaction notes

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