Formaldehyde → HCID 67815055, compound

HRID 1054544Notes

Reaction equation

HRID 1054544 reaction equation
C=O.[Cl:3][C:4]1[C:5]([C:50]([F:53])([F:52])[F:51])=[CH:6][C:7]2[N:11]=[C:10]([CH2:12][CH2:13][CH2:14][CH2:15][NH:16][CH2:17][C@@H:18]3[C@H:22]4[O:23][C:24]([CH3:27])([CH3:26])[O:25][C@H:21]4[C@H:20]([N:28]4[C:32]5[N:33]=[CH:34][N:35]=[C:36]([NH:37][CH:38]6[CH2:40][CH2:39]6)[C:31]=5[CH:30]=[CH:29]4)[CH2:19]3)[N:9]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[C:8]=2[CH:49]=1.[BH3-][C:55]#N.[Na+]>CO.C1COCC1>[Cl:3][C:4]1[C:5]([C:50]([F:53])([F:51])[F:52])=[CH:6][C:7]2[N:11]=[C:10]([CH2:12][CH2:13][CH2:14][CH2:15][N:16]([CH2:17][C@@H:18]3[C@H:22]4[O:23][C:24]([CH3:27])([CH3:26])[O:25][C@H:21]4[C@H:20]([N:28]4[C:32]5[N:33]=[CH:34][N:35]=[C:36]([NH:37][CH:38]6[CH2:39][CH2:40]6)[C:31]=5[CH:30]=[CH:29]4)[CH2:19]3)[CH3:55])[N:9]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[C:8]=2[CH:49]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 86705758HCID 86705758, compound

Product 1

HCID 67815055HCID 67815055, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

37% aq. Formaldehyde (54.07 uL, 0.722 mmol, 2 eq) was added to a solution of 7-[(3aS,4R,6R,6aR)-6-[({4-[6-chloro-5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]butyl}amino)methyl]-2,2-dimethyl-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-N-cyclopropyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (270 mg, 0.361 mmol, 1 eq) in MeOH:THF (1:1, 10 ml) at RT and stirred. NaCNBH3 was then added portionwise and continued stirring for 1 h. LCMS at 1 hr showed the reaction to be complete. The solvent was then removed in vacuo. The residue was dissolved in DCM (30 ml) and washed with water (30 ml) before drying over Na2SO4, filtering and evaporated. Purification by preparative TLC, eluting three times with MeOH:DCM (6:94) gave the desired product as a colorless oil (200 mg, 62%): MS (ESI+) for C37H51ClF3N7O3Si m/z 762.30 [M+H]+; HPLC purity 86% (ret. time, 1.75 min).

Workup

  1. stirringcontinued stirring for 1 h
  2. customthe reaction
  3. customThe solvent was then removed in vacuo
  4. dissolutionThe residue was dissolved in DCM (30 ml)
  5. washwashed with water (30 ml)
  6. dry with materialbefore drying over Na2SO4
  7. filtrationfiltering
  8. customevaporated
  9. customPurification by preparative TLC
  10. washeluting three times with MeOH:DCM (6:94)

Sources & evidence

ORD record
ord-c49224be02d34d2796b312a6073e345c
Source dataset
uspto-grants-2016_07
Patent number
US09394310B2

Reaction notes

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