Cesium carbonate → HCID 11361434, compound

HRID 2373904Notes

Reaction equation

HRID 2373904 reaction equation
[NH2:1][C:2]1[C:3]2[N:4]([C:8]([CH:18]3[CH2:21][CH2:20][CH2:19]3)=[N:9][C:10]=2[C:11]2[CH:12]=[C:13]([OH:17])[CH:14]=[CH:15][CH:16]=2)[CH:5]=[CH:6][N:7]=1.C([O-])([O-])=O.[Cs+].[Cs+].[C:28]([C:30]1[CH:37]=[CH:36][CH:35]=[CH:34][C:31]=1[CH2:32]Br)#[N:29]>CN(C=O)C>[NH2:1][C:2]1[C:3]2[N:4]([C:8]([CH:18]3[CH2:21][CH2:20][CH2:19]3)=[N:9][C:10]=2[C:11]2[CH:12]=[C:13]([CH:14]=[CH:15][CH:16]=2)[O:17][CH2:32][C:31]2[CH:34]=[CH:35][CH:36]=[CH:37][C:30]=2[C:28]#[N:29])[CH:5]=[CH:6][N:7]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 895992-(Bromomethyl)benzonitrileHCID 11716093HCID 11716093, compound

Product 1

HCID 11361434HCID 11361434, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 3-(8-Amino-3-cyclobutyl-imidazo[1,5-a]pyrazin-1-yl)-phenol (500 mg, 1.78 mmol) in DMF (8.9 mL) was charged with Cs2CO3 (871 mg, 2.68 mmol) and stirred for 30 min. at rt. A solution of 2-cyanobenzyl bromide (500 mg, 1.78 mmol) in DMF was added to the reaction mixture. After 24 h at rt the reaction mixture was concentrated in vacuo and chromatographed on silica gel [Jones Flashmaster, 10 g cartridge, eluting with 50% EtOAc:hexanes to 100% EtOAc]. The product was then recrystalized with CH2Cl2 and hexanes yielding the title compound as a light red solid; 1H NMR (CDCl3, 400 MHz) δ 2.02-2.06 (m, 1H), 2.11-2.33 (m, 1H), 2.45-2.53 (m, 2H), 2.59-2.69 (m, 2H), 3.77-3.86 (m, 1H), 5.33 (s, 2H), 7.02-7.04 (m, 1H), 7.05 (dd, J=2.4 Hz, 1H), 7.10 (d, J=5.2 Hz, 1H), 7.29-7.30 (m, 1H), 7.33 (q, J=3.6, 11H), 7.40-7.64 (m, 2H), 7.61-7.66 (m, 1H), 7.70-7.72 (m, 2H); MS (ES+): m/z 395.99 (100) [MH+].

Workup

  1. concentrationAfter 24 h at rt the reaction mixture was concentrated in vacuo
  2. customchromatographed on silica gel [Jones Flashmaster, 10 g cartridge, eluting with 50% EtOAc:hexanes to 100% EtOAc]
  3. customThe product was then recrystalized with CH2Cl2 and hexanes yielding the title compound as a light red solid

Sources & evidence

ORD record
ord-0aa7023298764604b1c682e2f6b2f181
Source dataset
uspto-grants-2008_12
Patent number
US07459554B2

Reaction notes

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