t-butyl (3-(6-amino-2-fluoro-8-((6-iodobenzo[d][1,3]dioxol-5-yl)methyl)-9H-purin-9-yl)propyl)carbamate → 9-(3-aminopropyl)-2-fluoro-8-((6-iodobenzo[d][1,3]dioxol-5-yl)methyl)-9H-purin-6-amine

HRID 527870Notes

Reaction equation

HRID 527870 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]([F:11])[N:8]=[C:7]2[C:3]=1[N:4]=[C:5]([CH2:23][C:24]1[C:32]([I:33])=[CH:31][C:27]3[O:28][CH2:29][O:30][C:26]=3[CH:25]=1)[N:6]2[CH2:12][CH2:13][CH2:14][NH:15]C(=O)OC(C)(C)C>C(O)(C(F)(F)F)=O.C(Cl)Cl>[NH2:15][CH2:14][CH2:13][CH2:12][N:6]1[C:5]([CH2:23][C:24]2[C:32]([I:33])=[CH:31][C:27]3[O:28][CH2:29][O:30][C:26]=3[CH:25]=2)=[N:4][C:3]2[C:7]1=[N:8][C:9]([F:11])=[N:10][C:2]=2[NH2:1]

Participants

3

Reactant 1

HCID 86713737t-butyl (3-(6-amino-2-fluoro-8-((6-iodobenzo[d][1,3]dioxol-5-yl)methyl)-9H-purin-9-yl)propyl)carbamate

Product 1

HCID 867137389-(3-aminopropyl)-2-fluoro-8-((6-iodobenzo[d][1,3]dioxol-5-yl)methyl)-9H-purin-6-amineYield 90.2%

Reagents, catalysts & solvents 1

HCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

To a solution of 2-fluoro-8-((6-iodobenzo[d][1,3]dioxol-5-yl)methyl)-9H-purin-6-amine (3.3 g, 8 mmol) in DMF (50 mL) was added t-butyl (3-bromopropyl)carbamate (9.6 g, 40 mmol) and Cs2CO3 (5.26 g, 16 mmol). The resulting mixture was stirred at room temperature for 1 day. The reaction mixture was condensed and purified by flash chromatography to yield t-butyl (3-(6-amino-2-fluoro-8-((6-iodobenzo[d][1,3]dioxol-5-yl)methyl)-9H-purin-9-yl)propyl)carbamate as white solid (3.1 g, 66%). The solution of t-butyl (3-(6-amino-2-fluoro-8-((6-iodobenzo[d][1,3]dioxol-5-yl)methyl)-9H-purin-9-yl)propyl)carbamate (1.9 g, 3.3 mmol) in the mixture of TFA/CH2Cl2 (10 mL/2 mL) was stirred at room temperature for 2 hrs. The reaction mixture was condensed, purified by flash chromatography to yield 9-(3-aminopropyl)-2-fluoro-8-((6-iodobenzo[d][1,3]dioxol-5-yl)methyl)-9H-purin-6-amine as yellow solid (1.4 g, 89%). 1H NMR (600 MHz, CDCl3/MeOH-d4): δ 7.28 (s, 1H), 6.70 (s, 1H), 5.98 (s, 2H), 4.21 (s, 2H), 4.13 (t, J=7.1 Hz, 2H), 2.67 (t, J=6.8 Hz, 2H), 1.89 (m, 2H); 13C NMR (150 MHz, CDCl3/MeOH-d4): δ 160.8, 159.4, 157.8, 153.7, 152.1, 150.4, 149.4, 132.4, 120.1, 117.2, 111.3, 103.4, 89.8, 41.7, 40.4, 39.3, 33.6; HRMS (ESI) m/z [M+H]+ calcd. for C16H17IFN6O2, 471.0436. found 471.0442.

Workup

  1. customcondensed
  2. custompurified by flash chromatography

Sources & evidence

ORD record
ord-f3a47ddac78841cf8afe788471a43ead
Source dataset
uspto-grants-2016_05
Patent number
US09346808B2

Reaction notes

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