Methanol → 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

HRID 511611Notes

Reaction equation

HRID 511611 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]([CH3:28])[CH:23]2[CH2:26][CH:25]([NH2:27])[CH2:24]2)[O:12]1.[C:29]([C:33]1[CH:38]=[CH:37][C:36]([N:39]=[C:40]=[O:41])=[CH:35][CH:34]=1)([CH3:32])([CH3:31])[CH3:30].CO>C1COCC1.C(Cl)Cl>[NH4+:1].[OH-:12].[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]([CH3:28])[CH:23]2[CH2:24][CH:25]([NH:27][C:40]([NH:39][C:36]3[CH:37]=[CH:38][C:33]([C:29]([CH3:32])([CH3:31])[CH3:30])=[CH:34][CH:35]=3)=[O:41])[CH2:26]2)[O:12]1

Participants

7

Reactant 3

HCID 887MethanolHCID 27356951-Tert-butyl-4-isocyanatobenzeneHCID 67776131N1-(((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

Product 2

HCID 14923Ammonium HydroxideHCID 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)ureaYield 137.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 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 (28 mg, 0.072 mmol) and TEA (22 mg, 0.22 mmol) in THF (3 mL) was added dropwise 1-tert-butyl-4-isocyanatobenzene (18 mg, 0.11 mmol) in DCM (0.5 mL). The reaction was stirred for 1 hour at room temperature. The reaction was concentrated and purified by Prep-TLC (twice, DCM:MeOH:NH4OH=300:30:8, V/V) to obtain the desired compound (28 mg, Yield: 88%) as pale white solid. 1H NMR (500 MHz, MeOD): δH 8.29 (s, 1H), 8.24 (s, 1H), 7.28-7.22 (m, 4H), 6.25 (d, J=2.5 Hz, 1H), 5.52-5.50 (m, 1H), 5.07-5.05 (m, 1H), 4.46-4.44 (m, 1H), 3.88-3.85 (m, 1H), 2.97 (brs, 1H), 2.80-2.78 (m, 2H), 2.48-2.42 (m, 2H), 2.30 (s, 3H), 1.84-1.82 (m, 1H), 1.60 (s, 3H), 1.58-1.56 (m, 1H), 1.39 (s, 3H), 1.28 (s, 9H) ppm; ESI-MS (m/z): 565.3 [M+1]+.

Workup

  1. concentrationThe reaction was concentrated
  2. custompurified by Prep-TLC (twice, DCM

Sources & evidence

ORD record
ord-2ef22f49187e42cf81abe729caaff097
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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