1,1-Dichloroethane → [3-Methyl-4-(pyridin-3-yloxy)-phenyl]-(6-piperidin-4-ylethynyl-quinazolin-4-yl)-amine

HRID 2055151Notes

Reaction equation

HRID 2055151 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]#[C:15][C:16]2[CH:17]=[C:18]3[C:23](=[CH:24][CH:25]=2)[N:22]=[CH:21][N:20]=[C:19]3Cl)[CH2:10][CH2:9]1)=O)(C)(C)C.[CH3:27][C:28]1[CH:29]=[C:30]([NH2:41])[CH:31]=[CH:32][C:33]=1[O:34][C:35]1[CH:36]=[N:37][CH:38]=[CH:39][CH:40]=1.ClC(Cl)C>C(O)(C)(C)C>[CH3:27][C:28]1[CH:29]=[C:30]([NH:41][C:19]2[C:18]3[C:23](=[CH:24][CH:25]=[C:16]([C:15]#[C:14][CH:11]4[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]4)[CH:17]=3)[N:22]=[CH:21][N:20]=2)[CH:31]=[CH:32][C:33]=1[O:34][C:35]1[CH:36]=[N:37][CH:38]=[CH:39][CH:40]=1

Participants

5

Reactant 3

HCID 63651,1-DichloroethaneHCID 155504831-Boc-4-(4-Chloroquinazolin-6-ylethynyl)piperidineHCID 219252673-Methyl-4-(pyridin-3-yloxy)aniline

Product 1

HCID 10160134[3-Methyl-4-(pyridin-3-yloxy)-phenyl]-(6-piperidin-4-ylethynyl-quinazolin-4-yl)-amineYield 105%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Procedure

4-(4-Chloro-quinazolin-6-ylethynyl)-piperidine-1-carboxylic acid tert-butyl ester (80 mg, 0.21 mmol) and 3-Methyl-4-(pyridin-3-yloxy)-phenylamine (43 mg, 0.21 mmol) were mixed together in tert-butanol (1 mL) and dichloroethane (1 mL) and heated in a sealed vial at 90° C. for 20 minutes. The reaction was cooled down and HCl (gas) was bubbled through for 5 minutes. EtOAC was then added whereupon yellow precipitation occurred. The precipitate was collected and dried to afford the desired product [3-Methyl-4-(pyridin-3-yloxy)-phenyl]-(6-piperidin-4-ylethynyl-quinazolin-4-yl)-amine as a yellow solid (96 mg, 95%). 1H NMR (CDCl3) δ 2.01 ((m, 2H), 2.22 (m, 2H), 2.35(s, 3H), 3.20 (m, 2H), 3.45(m, 2H), 7.28 (d, 1H, J=8.7 Hz), 7.75(dd, 3H, J1=8.7, J2=8.7 Hz), 8.06 (dd, J=8.7), 8.10 (dd, J1=J2=8.7 Hz), 8.17 (m, 1H), 8.60 (d, 1H, J=5.4 Hz), 8.80 (s, 1H), 8.89 (s, 1H). MS: M+1, 436.6.

Workup

  1. temperatureThe reaction was cooled down
  2. customHCl (gas) was bubbled through for 5 minutes
  3. additionEtOAC was then added whereupon yellow precipitation
  4. customThe precipitate was collected
  5. customdried

Sources & evidence

ORD record
ord-46c347f86b704510ad4c76cfc52fed1d
Source dataset
uspto-grants-2008_02
Patent number
US07332493B2

Reaction notes

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