Lithium hydroxide, monohydrate → 3-(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)(isopropyl)amino)cyclobutyl)propanoic acid

HRID 511687Notes

Reaction equation

HRID 511687 reaction equation
[CH3:1][O:2][C:3]1[CH:50]=[C:49]([O:51][CH3:52])[CH:48]=[CH:47][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]([CH:44]([CH3:46])[CH3:45])[CH:28]4[CH2:31][CH:30]([CH2:32][CH2:33][C:34]([O:36]CC5C=CC=CC=5)=[O:35])[CH2:29]4)[O:17]3)[C:9]=2[N:10]=[CH:11][N:12]=1.O[Li].O>C1COCC1.CO.O>[CH3:1][O:2][C:3]1[CH:50]=[C:49]([O:51][CH3:52])[CH:48]=[CH:47][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]([CH:44]([CH3:45])[CH3:46])[CH:28]4[CH2:29][CH:30]([CH2:32][CH2:33][C:34]([OH:36])=[O:35])[CH2:31]4)[O:17]3)[C:9]=2[N:10]=[CH:11][N:12]=1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 67776124benzyl 3-(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)(isopropyl)amino)cyclobutyl)propanoate

Product 1

HCID 677769633-(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)(isopropyl)amino)cyclobutyl)propanoic acidYield 123%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
30 °C

Procedure

To a solution of benzyl 3-(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)(isopropyl)amino)cyclobutyl)propanoate (2.7 g, 3.78 mmol) in THF/MeOH (15 mL/15 mL) was added a solution of LiOH.H2O (1.6 g, 37.82 mmol) in water (5 mL). The mixture was stirred at 30° C. for 2 h. The volatiles were removed under reduced pressure. To the residue was diluted with water (10 mL) and extracted with EA (15 mL×2). The suspension water layers were adjusted to pH=3-4 with 1 N HCl solution and extracted with EA (30 mL×3). The combined organic layers were washed with brine (50 in L). The organic phase was dried over Na2SO4, filtered and concentrated to afford the desired compound as a yellow solid (2.9 g). 1H NMR (500 MHz, MeOD): δH 8.20 (s, 1H), 7.92 (s, 0.5H), 7.38-7.32 (m, 3H), 7.28-7.23 (m, 1.5H), 7.14 (d, J=8.5 Hz, 1H), 6.68 (brs, 1H), 6.56 (d, J=2.0 Hz, 1H), 6.44 (d, J=8.5 Hz, 1H), 6.25 (s, 1H), 5.51-5.47 (m, 1H), 5.18-5.13 (m, 1H), 4.66 (s, 2H), 4.61 (s, 1H), 4.43-4.40 (m, 1H), 3.96-3.90 (m, 0.5H), 3.85 (s, 3H), 3.77 (s, 3H), 3.65-3.58 (m, 0.5H), 3.50-3.40 (m, 2H), 2.46-2.36 (m, 1H), 2.20-2.00 (m, 4H), 1.98-1.70 (m, 2.5H), 1.70-1.58 (m, 4.5H), 1.40 (s, 3H), 1.18 (d, J=5.0 Hz, 3H), 0.90 (t, J=6.0 Hz, 3H) ppm; ESI-MS (m/z): 624.3 [M+1]+.

Workup

  1. customThe volatiles were removed under reduced pressure
  2. additionTo the residue was diluted with water (10 mL)
  3. extractionextracted with EA (15 mL×2)
  4. extractionextracted with EA (30 mL×3)
  5. washThe combined organic layers were washed with brine (50 in L)
  6. dry with materialThe organic phase was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-3f6b9eaa3521407db4136c3eb5aa91b5
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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