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)methyl)-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)methyl)-3-(4-(tert-butyl)phenyl)urea

HRID 2040627Notes

Reaction equation

HRID 2040627 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]([CH3:42])[CH:23]2[CH2:26][CH:25]([CH2:27][NH:28][C:29]([NH:31][C:32]3[CH:37]=[CH:36][C:35]([C:38]([CH3:41])([CH3:40])[CH3:39])=[CH:34][CH:33]=3)=[O:30])[CH2:24]2)[O:12]1>Cl.CO>[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]([CH3:42])[CH:23]2[CH2:26][CH:25]([CH2:27][NH:28][C:29]([NH:31][C:32]3[CH:33]=[CH:34][C:35]([C:38]([CH3:41])([CH3:39])[CH3:40])=[CH:36][CH:37]=3)=[O:30])[CH2:24]2)[C@@H:14]([OH:18])[C@H:15]1[OH:16]

Participants

3

Reactant 1

HCID 677761471-((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)methyl)-3-(4-(tert-butyl)phenyl)urea

Product 1

HCID 677746111-((3-((((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)(methyl)amino)cyclobutyl)methyl)-3-(4-(tert-butyl)phenyl)ureaYield 25%

Reagents, catalysts & solvents 1

HCID 21893726Hydrochloride methanolSolvent

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)methyl)-3-(4-(tert-butyl)phenyl)urea (55 mg) in HCl/MeOH (2.5 mol/L) (2 mL) was stirred at RT for 2 h and then concentrated to dryness. K2CO3 (52 mg) in water (0.5 mL) and MeOH (5 mL) was added. The resulting mixture was stirred for another 10 min at RT, filtered and the filtrate was concentrated. The residue was purified by preparative-HPLC to give Compound 110 (10 mg, yield: 25%) as a white solid. 1HNMR (500 MHz, MeOD): δH 8.26 (s, 1H), 8.18 (s, 1H), 7.26-7.19 (m, 4H), 5.96 (d, J=4.5 Hz, 1H), 4.674-4.655 (m, 1H), 4.24-4.16 (m, 2H), 3.15 (d, J=5.0 Hz, 2H), 2.83-2.73 (m, 3H), 2.20-1.59 (m, 8H), 1.26 (s, 9H) ppm; ESI-MS (m/z): 539.3 [M+1]+.

Workup

  1. concentrationconcentrated to dryness
  2. additionK2CO3 (52 mg) in water (0.5 mL) and MeOH (5 mL) was added
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated
  5. customThe residue was purified by preparative-HPLC

Sources & evidence

ORD record
ord-9b7df0c2d6e94a749855aa11bef4d173
Source dataset
uspto-grants-2013_11
Patent number
US08580762B2

Reaction notes

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