1-(3-((((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutyl)-3-(4-(tert-butyl)phenyl)urea → 1-(3-((((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)(methyl)amino)cyclobutyl)-3-(4-(tert-butyl)phenyl)urea

HRID 511612Notes

Reaction equation

HRID 511612 reaction equation
[NH2:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C@H:11]1[C@@H:15]2[O:16]C(C)(C)[O:18][C@@H:14]2[C@@H:13]([CH2:21][N:22]([CH3:41])[CH:23]2[CH2:26][CH:25]([NH:27][C:28]([NH:30][C:31]3[CH:36]=[CH:35][C:34]([C:37]([CH3:40])([CH3:39])[CH3:38])=[CH:33][CH:32]=3)=[O:29])[CH2:24]2)[O:12]1>C(O)(C(F)(F)F)=O.O>[NH2:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C@@H:11]1[O:12][C@H:13]([CH2:21][N:22]([CH3:41])[CH:23]2[CH2:26][CH:25]([NH:27][C:28]([NH:30][C:31]3[CH:36]=[CH:35][C:34]([C:37]([CH3:38])([CH3:39])[CH3:40])=[CH:33][CH:32]=3)=[O:29])[CH2:24]2)[C@@H:14]([OH:18])[C@H:15]1[OH:16]

Participants

4

Reactant 1

HCID 677772951-(3-((((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutyl)-3-(4-(tert-butyl)phenyl)urea

Product 1

HCID 677758951-(3-((((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)(methyl)amino)cyclobutyl)-3-(4-(tert-butyl)phenyl)ureaYield 65%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of 1-(3-((((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutyl)-3-(4-(tert-butyl)phenyl)urea (125 mg, 0.23 mmol) in TFA (0.90 mL) and 0.10 mL of water were stirred for 1 hour at room temperature. The reaction was concentrated to dryness, dissolved in MeOH (5 mL) and K2CO3 (60 mg) in 0.5 mL of water was added dropwise. The reaction was stirred at rt for 0.5 h and concentrated to obtain the residue which was purified by prep-TLC (DCM:MeOH:NH4OH=300:30:8, V/V) to obtain the desired compound (75 mg, Yield: 65%) as pale white solid. 1H NMR (500 MHz, MeOD): δH 8.27 (s, 1H), 8.21 (s, 1H), 7.28-7.20 (m, 4H), 6.00-5.99 (m, 1H), 4.77-4.75 (m, 1H), 4.28-4.23 (m, 2H), 3.92-3.88 (m, 1H), 2.92 (brs, 1H), 2.83-2.81 (m, 2H), 2.59-2.56 (m, 2H), 2.32 (s, 3H), 1.74-1.64 (m, 2H), 1.27 (s, 9H) ppm; ESI-MS (m/z): 525.3 [M+1]+.

Workup

  1. concentrationThe reaction was concentrated to dryness
  2. dissolutiondissolved in MeOH (5 mL)
  3. additionK2CO3 (60 mg) in 0.5 mL of water was added dropwise
  4. concentrationconcentrated
  5. customto obtain the residue which
  6. customwas purified by prep-TLC (DCM:MeOH:NH4OH=300:30:8, V/V)

Sources & evidence

ORD record
ord-e67505a66b6243bca77339169b53b379
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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