Water → (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 methanesulfonate

HRID 511583Notes

Reaction equation

HRID 511583 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:17]([CH3:20])([CH3:19])[O:18][C@@H:14]2[C@@H:13]([CH2:21][N:22]([CH3:29])[CH:23]2[CH2:26][CH:25]([CH2:27][OH:28])[CH2:24]2)[O:12]1.CCN(CC)CC.[CH3:37][S:38](Cl)(=[O:40])=[O:39].O>C(Cl)Cl>[CH3:37][S:38]([O:28][CH2:27][CH:25]1[CH2:24][CH:23]([N:22]([CH2:21][C@@H:13]2[C@@H:14]3[C@@H:15]([O:16][C:17]([CH3:19])([CH3:20])[O:18]3)[C@H:11]([N:6]3[CH:5]=[N:4][C:3]4[C:7]3=[N:8][CH:9]=[N:10][C:2]=4[NH2:1])[O:12]2)[CH3:29])[CH2:26]1)(=[O:40])=[O:39]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 67777452(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)methanol

Product 1

HCID 86666107(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 methanesulfonateYield 35%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of (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)methanol taken directly from the previous step in DCM (25 ml) was added Et3N (467 mg, 4.62 mmol) and MsCl (264 mg, 2.31 mmol) as a solution in DCM (5 ml). The mixture was stirred for 2 h. Water (20 ml) and DCM (30 ml×2) was added. The organic layer was dried over Na2SO4 and concentrated, purified with Prep-TLC (DCM:MeOH=10:1) to give the title compound (390 mg, Yield 35% for two steps). 1H NMR (500 MHz, MeOD): δH 8.27 (s, 1H), 8.21 (s, 1H), 6.203-6.200 (m, 1H), 5.529 (dd, J=2.0, 7.0 Hz, 1H), 5.010 (dd, J=3.0, 6.0 Hz, 1H), 4.354 (dd, J=3.5, 8.0 Hz, 1H), 4.197-4.182 (m, 2H), 3.585 (brs, 1H), 3.073-2.948 (m, 5H), 2.595-2.513 (m, 2H), 2.394 (brs, 1H), 2.207 (brs, 1H), 2.107 (s, 3H), 2.030-1.989 (m, 1H), 1.840-1.811 (m, 2H), 1.586 (s, 3H), 1.390 (brs, 1H), 1.329-1.280 (m, 6H), 0.905-0.878 (m, 1H) ppm; ESI-MS (m/z): 483.3[M+1]+.

Workup

  1. dry with materialThe organic layer was dried over Na2SO4
  2. concentrationconcentrated
  3. custompurified with Prep-TLC (DCM:MeOH=10:1)

Sources & evidence

ORD record
ord-1427bafae53d4b69b92b1ec1178ffa29
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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