Acetic Acid → methyl 2-(3-((((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutyl)acetate

HRID 511591Notes

Reaction equation

HRID 511591 reaction equation
[CH3:1][O:2][C:3]1[CH:40]=[C:39]([O:41][CH3:42])[CH:38]=[CH:37][C:4]=1[CH2:5][NH:6][C:7]1[C:8]2[CH:15]=[CH:14][N:13]([C@H:16]3[C@@H:20]4[O:21][C:22]([CH3:25])([CH3:24])[O:23][C@@H:19]4[C@@H:18]([CH2:26][NH:27][CH:28]4[CH2:31][CH:30]([CH2:32][C:33]([O:35][CH3:36])=[O:34])[CH2:29]4)[O:17]3)[C:9]=2[N:10]=[CH:11][N:12]=1.[C:43]([BH3-])#N.[Na+].C(O)(=O)C.C=O>CO>[CH3:1][O:2][C:3]1[CH:40]=[C:39]([O:41][CH3:42])[CH:38]=[CH:37][C:4]=1[CH2:5][NH:6][C:7]1[C:8]2[CH:15]=[CH:14][N:13]([C@H:16]3[C@@H:20]4[O:21][C:22]([CH3:24])([CH3:25])[O:23][C@@H:19]4[C@@H:18]([CH2:26][N:27]([CH3:43])[CH:28]4[CH2:29][CH:30]([CH2:32][C:33]([O:35][CH3:36])=[O:34])[CH2:31]4)[O:17]3)[C:9]=2[N:10]=[CH:11][N:12]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 67775569methyl 2-(3-((((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydro furo[3,4-d][1,3]dioxol-4-yl)methyl)amino)cyclobutyl)acetate

Product 1

HCID 67777497methyl 2-(3-((((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutyl)acetateYield 100%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A solution of methyl 2-(3-((((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)amino)cyclobutyl)acetate (267 mg, 0.459 mmol) in methanol (12 mL) was treated with sodium cyanoborohydride (380 mg, 6.1 mmol). The pH of the solution was adjusted to ˜6 by the dropwise addition of a 10% (v/v) solution of glacial acetic acid in methanol. The mixture was treated with 37% formaldehyde (0.57 mL, 7.6 mmol) dropwise and the mixture was stirred at room temperature for 1 h at which time, HPLC indicated the starting material was consumed. The reaction mixture was concentrated to remove the methanol. The aqueous solution that remained was diluted with 25 mL NaHCO3 and the aqueous phase was extracted with three 20 mL portions of CH2Cl2. The organic phase was washed with 20 mL sat NaHCO3, dried over Na2SO4, filtered and concentrated to yield the title compound (272 mg, 100%) as a colorless stiff foam which was found to be of sufficient purity for use in the next step: MS (ESI+) for C31H41N5O7 m/z 596.5 (M+H)+; HPLC purity >95% (ret. time, 2.89 min).

Workup

  1. customwas consumed
  2. concentrationThe reaction mixture was concentrated
  3. customto remove the methanol
  4. additionThe aqueous solution that remained was diluted with 25 mL NaHCO3
  5. extractionthe aqueous phase was extracted with three 20 mL portions of CH2Cl2
  6. washThe organic phase was washed with 20 mL
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-8a9ac7f5c0f448748104e90088ede704
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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