2-Chloroquinazoline → HCID 178516969, compound

HRID 707391Notes

Reaction equation

HRID 707391 reaction equation
Cl.[NH2:2][C@H:3]1[CH2:6][C@H:5]([N:7]2[C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[N:9]([CH:16]3[CH2:18][CH2:17]3)[C:8]2=[O:19])[CH2:4]1.CCN(C(C)C)C(C)C.Cl[C:30]1[N:39]=[CH:38][C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[N:31]=1>CS(C)=O.CCOC(C)=O>[CH:16]1([N:9]2[C:10]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[N:7]([C@H:5]3[CH2:6][C@H:3]([NH:2][C:30]4[N:39]=[CH:38][C:37]5[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=5)[N:31]=4)[CH2:4]3)[C:8]2=[O:19])[CH2:17][CH2:18]1

Participants

6

Reactant 3

HCID 740542-ChloroquinazolineHCID 81531DiisopropylethylamineHCID 178479282HCID 178479282, compound

Product 1

HCID 178516969HCID 178516969, compoundYield 37%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 3-(trans-3-aminocyclobutyl)-1-cyclopropyl-1H-imidazo[4,5-b]pyridin-2(3H)-one hydrochloride (0.458 g, 1.63 mmol), Hunig's base (Aldrich, 1.139 ml, 6.52 mmol), and 2-chloroquinazoline (Waterstone, 0.322 g, 1.956 mmol) in DMSO (3.26 ml) was heated to 120° C. overnight. The reaction mixture was diluted with EtOAc and washed with water and brine. Purification by Biotage (0-100% EtOAc/hexane, 25 g Biotage column) produced 1-cyclopropyl-3-(trans-3-(quinazolin-2-ylamino)cyclobutyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one (0.244 g, 0.601 mmol, 37% yield). M+1: 373.0. 1H NMR (300 MHz, MeOH) δ ppm 0.93-1.03 (m, 3 H) 1.06-1.19 (m, 3 H) 2.47-2.64 (m, 2 H) 2.85-3.00 (m, 2 H) 3.42-3.60 (m, 2 H) 5.25-5.45 (m, 1 H) 7.04-7.20 (m, 1 H) 7.20-7.35 (m, 1 H) 7.48-7.64 (m, 3 H) 7.64-7.83 (m, 3 H) 7.99-8.14 (m, 1 H) 8.99-9.12 (m, 1 H).

Workup

  1. washwashed with water and brine
  2. customPurification by Biotage (0-100% EtOAc/hexane, 25 g Biotage column)

Sources & evidence

ORD record
ord-229852ba54ed48ba8262330b06065a41
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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