Hydrochloric Acid → 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)acetic acid

HRID 511592Notes

Reaction equation

HRID 511592 reaction equation
[CH3:1][O:2][C:3]1[CH:41]=[C:40]([O:42][CH3:43])[CH:39]=[CH:38][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][N:27]([CH3:37])[CH:28]4[CH2:31][CH:30]([CH2:32][C:33]([O:35]C)=[O:34])[CH2:29]4)[O:17]3)[C:9]=2[N:10]=[CH:11][N:12]=1.[OH-].[Na+].O.Cl>CO>[CH3:1][O:2][C:3]1[CH:41]=[C:40]([O:42][CH3:43])[CH:39]=[CH:38][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]([CH3:37])[CH:28]4[CH2:29][CH:30]([CH2:32][C:33]([OH:35])=[O:34])[CH2:31]4)[O:17]3)[C:9]=2[N:10]=[CH:11][N:12]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14798Sodium HydroxideHCID 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)acetate

Product 1

HCID 677748662-(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)acetic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

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)(methyl)amino)cyclobutyl)acetate (270 mg, 0.453 mmol) in methanol (8.6 mL) was treated dropwise with a solution of sodium hydroxide (36 mg, 0.91 mmol) in water (0.9 mL, 50 mmol) and the mixture was heated at 50° C. After 17 h, HPLC indicated the reaction was complete. The reaction mixture was cooled to room temperature and treated with 0.91 mL 1.0N HCl to adjust the pH to ˜7. The solution was concentrated to remove the methanol and the resulting aqueous suspension was lyophilized to yield a white solid. The material was used as is in the next step, assuming a quantitative recovery: MS (ESI+) for C30H39N5O7 m/z 582.4 (M+H)+; MS (ESI−) for C30H39N5O7 m/z 580.4 (M−H)−; HPLC purity >95% (ret. time, 2.72 min).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationThe solution was concentrated
  3. customto remove the methanol
  4. customto yield a white solid
  5. customHPLC purity >95% (ret. time, 2.72 min)

Sources & evidence

ORD record
ord-8802d1ac842e4f10a54bdcfe6fed0921
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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