1-Ethynyl-2-methylcyclohexanol → 5-[6-Amino-2-(1-hydroxy-2-methyl-cyclohexylethynyl)-purin-9-yl]-3,4-dihydroxytetrahydrofuran-2-carboxylic acid ethylamide

HRID 16066Notes

Reaction equation

HRID 16066 reaction equation
[C:1]([C:3]1([OH:10])[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[CH3:9])#[CH:2].[CH3:11][CH2:12][NH:13][C:14]([C@H:16]1[O:20][C@@H:19]([N:21]2[C:25]3[N:26]=[C:27](I)[N:28]=[C:29]([NH2:30])[C:24]=3[N:23]=[CH:22]2)[CH:18]([OH:32])[C@H:17]1[OH:33])=[O:15]>>[CH2:12]([NH:13][C:14]([CH:16]1[CH:17]([OH:33])[CH:18]([OH:32])[CH:19]([N:21]2[CH:22]=[N:23][C:24]3[C:25]2=[N:26][C:27]([C:2]#[C:1][C:3]2([OH:10])[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]2[CH3:9])=[N:28][C:29]=3[NH2:30])[O:20]1)=[O:15])[CH3:11]

Participants

3

Reactant 2

HCID 858701-Ethynyl-2-methylcyclohexanolHCID 45039581(2S,3R,5R)-5-(6-Amino-2-iodo-9H-purin-9-yl)-N-ethyl-3,4-dihydroxyoxolane-2-carboxamide

Product 1

HCID 102254725-[6-Amino-2-(1-hydroxy-2-methyl-cyclohexylethynyl)-purin-9-yl]-3,4-dihydroxytetrahydrofuran-2-carboxylic acid ethylamideYield 65%

Procedure

The reaction of 1-Ethynyl-2-methyl-cyclohexanol (JR3169B) (100 mg, 0.72 mmol) with 2-iodo-NECA (25 mg, 0.06 mmol) under the general coupling conditions gave JR3177A (8.0 mg) and JR3177B (8.2 mg) (overall yield 65%) as white solids after purification by a silica plug and RP-HPLC. JR3177A: 1H NMR (CD3OD-d4) δ 8.47 (s, 1 H), 6.05 (d, J=6.9 Hz, 1 H), 4.77 (dd, J=6.9 Hz, J=4.9 Hz, 1 H), 4.45 (d, J=1.9 Hz, 1 H), 4.34 (dd, J=4.6 Hz, J=2.1 Hz, 1 H), 3.41 (m, 2 H), 2.13 (d, J=12.7 Hz, 2 H), 1.65 (m, 5 H), 1.32 (m, 2 H), 1.14 (t, J=7.0 Hz, 3 H), 1.13 (d, J=6.6 Hz, 3 H). 13C NMR (CD3OD-d4) δ. APCI m/z (rel intensity) 445.3 (MH+, 100), 427.4 (80), 254.4 (14). 1H NMR (CD3OD-d4) δ 8.49 (s, 1 H), 6.05 (d, J=6.9 Hz, 1 H), 4.78 (dd, J=6.4 Hz, J=4.9 Hz, 1 H), 4.45 (d, J=1.9 Hz, 1 H), 4.34 (dd, J=4.6 Hz, J=1.6 Hz, 1 H), 3.42 (m, 2 H), 2.12 (d, J=12.3 Hz, 2 H), 1.65 (m, 4 H), 1.35 (m, 4 H), 1.14 (t, J=7.3 Hz, 3 H), 1.12 (d, J=6.6 Hz, 3 H). 13C NMR (CD3OD-d4) δ. APCI m/z (rel intensity) 445.7 (MH+, 100), 427.3 (35), 254.4 (3.5).

Workup

  1. customgave JR3177A (8.0 mg) and JR3177B (8.2 mg) (overall yield 65%) as white solids
  2. customafter purification by a silica plug and RP-HPLC

Sources & evidence

ORD record
ord-20482741560643b193a7d973467fbff2
Source dataset
uspto-grants-2010_06
Patent number
US07737127B2

Reaction notes

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