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

HRID 1054558Notes

Reaction equation

HRID 1054558 reaction equation
[O-]S([O-])(=O)=O.[Mg+2].[NH2:7][CH2:8][C@@H:9]1[C@H:13]2[O:14][C:15]([CH3:18])([CH3:17])[O:16][C@H:12]2[C@H:11]([N:19]2[C:23]3[N:24]=[CH:25][N:26]=[C:27]([NH:28][CH:29]4[CH2:31][CH2:30]4)[C:22]=3[CH:21]=[CH:20]2)[CH2:10]1.[Cl:32][C:33]1[C:34]([C:55]([F:58])([F:57])[F:56])=[CH:35][C:36]2[N:40]=[C:39]([CH2:41][CH2:42][CH2:43][CH:44]=O)[N:38]([CH2:46][O:47][CH2:48][CH2:49][Si:50]([CH3:53])([CH3:52])[CH3:51])[C:37]=2[CH:54]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl>[Cl:32][C:33]1[C:34]([C:55]([F:58])([F:56])[F:57])=[CH:35][C:36]2[N:40]=[C:39]([CH2:41][CH2:42][CH2:43][CH2:44][NH:7][CH2:8][C@@H:9]3[C@H:13]4[O:14][C:15]([CH3:17])([CH3:18])[O:16][C@H:12]4[C@H:11]([N:19]4[C:23]5[N:24]=[CH:25][N:26]=[C:27]([NH:28][CH:29]6[CH2:31][CH2:30]6)[C:22]=5[CH:21]=[CH:20]4)[CH2:10]3)[N:38]([CH2:46][O:47][CH2:48][CH2:49][Si:50]([CH3:52])([CH3:51])[CH3:53])[C:37]=2[CH:54]=1

Participants

6

Reactant 4

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 5049666Sodium triacetoxyborohydrideHCID 67816524HCID 67816524, compoundHCID 86705755HCID 86705755, compound

Product 1

HCID 86705758HCID 86705758, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

MgSO4 (1.08 g, 9.0 mmol) was added to a solution of 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 (330 mg, 0.96 mmol) and 4-[6-chloro-5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]butanal (526 mg, 0.90 mmol) in DCE (10 ml) and stirred at RT for 15 mins. NaBH(OAc)3 (267 mg, 1.26 mmol) was then added to the reaction mixture and stirred for 1 hr. LC MS indicated complete consumption of the amine. Sat. NaHCO3 (20 ml) was 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 (1:199-3:97) afforded the desired product as an off white/pink foamy solid (278 mg, 41%); MS (ESI+) for C36HClF3N7O3Si m/z 748.05 [M+H]+; HPLC purity 84% (ret. Time, 1.73 min). 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 8.30 (1H, s), 7.39-8.21 (2H, m), 6.84-7.17 (1H, m), 6.63 (1H, br. s.), 5.43-5.55 (2H, m), 5.33-5.41 (1H, m), 4.82-5.14 (2H, m), 4.54 (1H, t, J=6.23 Hz), 3.53 (4H, dd, J=16.16, 8.12 Hz), 2.89-3.13 (3H, m), 2.82 (1H, d, J=7.41 Hz), 2.66-2.80 (2H, m), 2.45 (1H, s), 2.24-2.39 (1H, m), 2.18 (1H, s), 1.83-2.06 (2H, m), 1.63-1.73 (2H, m), 1.55-1.61 (3H, m), 1.30 (3H, s), 0.81-1.03 (4H, m), 0.56-0.78 (2H, m), −0.22-0.12 (9H, m).

Workup

  1. stirringstirred for 1 hr
  2. customconsumption of the amine
  3. additionSat. NaHCO3 (20 ml) was added to the reaction mixture
  4. extractionThe product was extracted with DCM (2×30 ml)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customPurification by silica gel column chromatography
  9. washeluting with 7N NH3 in MeOH:DCM (1:199-3:97)

Sources & evidence

ORD record
ord-eac1bae04f054d22966cc9bcc3f1dabb
Source dataset
uspto-grants-2016_07
Patent number
US09394310B2

Reaction notes

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