Dichloromethane → N1-(((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)-N1-methylcyclobutane-1,3-diamine

HRID 511610Notes

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]([CH3:38])[CH:23]2[CH2:26][CH:25]([NH:27]C(=O)OCC3C=CC=CC=3)[CH2:24]2)[O:12]1.C(Cl)Cl>CO.[OH-].[OH-].[Pd+2]>[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]([CH3:19])([CH3:20])[O:18][C@@H:14]2[C@@H:13]([CH2:21][N:22]([CH3:38])[CH:23]2[CH2:24][CH:25]([NH2:27])[CH2:26]2)[O:12]1

Participants

Conditions

Temperature: 35 °C

Procedure

To a solution of benzyl (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)carbamate (190 mg, 0.17 mmol) and Pd(OH)2 (14 mg, 0.1 mmol) in MeOH (5 mL) was charged with H2. The reaction was stirred at 35° C. for 5 h. The reaction was filtered with Celite and concentrated to dryness. The residue was purified by prep-TLC (DCM:MeOH=10:1) to the desired compound (28 mg, yield 42%). 1HNMR (500 MHz, MeOD): δH 8.29 (s, 1H), 8.21 (s, 1H), 6.19 (d, J=2.0 Hz, 1H), 5.51 (dd, J=6.5 and 2.0 Hz, 1H), 5.00 (dd, J=6.0 and 3.5 Hz, 1H), 4.34 (d, J=8.5 Hz, 1H), 3.14-3.11 (m, 1H), 2.60-2.57 (m, 1H), 2.52-2.48 (m, 2H), 2.34-2.31 (m, 2H), 2.10 (s, 3H), 1.66 (q, J=10.0 Hz, 1H), 1.58 (s, 3H), 1.48 (q, J=10.0 Hz, 1H), 1.37 (s, 3H) ppm; ESI-MS (m/z): 390.2[M+1]+.

Workup

filtrationThe reaction was filtered with Celite
concentrationconcentrated to dryness

Sources & evidence

ORD record: ord-4530572547384287a10e75693f8a3338
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09096634B2

Reaction notes

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