1,2-Dichloroethane → [6,7-Bis-(2-methoxy-ethoxy)-quinazolin-4-yl]-[3-methyl-4-(piperidin-4-yloxy)-phenyl]-amine hydrochloride

HRID 731902Notes

Reaction equation

HRID 731902 reaction equation
[Cl:1]CCCl.Cl[C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:21][CH2:22][CH2:23][O:24][CH3:25])=[C:13]([O:16][CH2:17][CH2:18][O:19][CH3:20])[CH:14]=2)[N:9]=[CH:8][N:7]=1.C(OC([N:33]1[CH2:38][CH2:37][CH:36]([O:39][C:40]2[CH:45]=[CH:44][C:43]([NH2:46])=[CH:42][C:41]=2[CH3:47])[CH2:35][CH2:34]1)=O)(C)(C)C>C(O)(C)(C)C>[ClH:1].[CH3:20][O:19][CH2:18][CH2:17][O:16][C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][C:12]=1[O:21][CH2:22][CH2:23][O:24][CH3:25])[N:9]=[CH:8][N:7]=[C:6]2[NH:46][C:43]1[CH:44]=[CH:45][C:40]([O:39][CH:36]2[CH2:37][CH2:38][NH:33][CH2:34][CH2:35]2)=[C:41]([CH3:47])[CH:42]=1

Participants

5

Reactant 3

HCID 111,2-DichloroethaneHCID 112899424-Chloro-6,7-bis(2-methoxyethoxy)quinazolineHCID 22181171Tert-butyl 4-(4-amino-2-methylphenoxy)piperidine-1-carboxylate

Product 1

HCID 69051900[6,7-Bis-(2-methoxy-ethoxy)-quinazolin-4-yl]-[3-methyl-4-(piperidin-4-yloxy)-phenyl]-amine hydrochlorideYield 99%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 1,2-dichloroethane (20 mL) and tert-butylalcohol was added 4-chloro-6,7-bis-(2-methoxy-ethoxy)-quinazoline and 4-(4-amino-2-methyl-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester. The reaction was heated at 90° C. for 1 hour. The reaction was cooled to room temperature then hydrogen chloride gas was bubbled in for 10 minutes. Ethyl acetate (30 mL) was added then cooled to 0° C. for 30 minutes. The solids were filtered and rinsed with ethyl acetate. Light yellow solids were further dried in a vacuum oven yielding the mono hydrochloride salt (1.91 g, 99%). 1H NMR (400 MHz, DMSO-d6) δ 11.42(s, 1H), 9.15(bs, 1H), 9.05(bs, 1H), 8.72(s, 1H), 8.40(s, 1H), 7.41(d, J=17.03 Hz, 2H), 7.40(d, J=2.49 Hz, 1H), 7.08(d, J=8.30 Hz, 1H), 4.67(m, 1H), 4.34(t, J=9.14, 4.98 Hz, 2H), 4.27(t, J=8.72, 4.56 Hz, 2H), 3.74(t, J=5.81, 3.32, 4H), 3.16(m, 2H), 3.07(m, 2H), 2.18(s, 3H), 2.10(m, 2H), LRMS (M+): 483.3, (M−): 481.3).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customhydrogen chloride gas was bubbled in for 10 minutes
  3. additionEthyl acetate (30 mL) was added
  4. temperaturethen cooled to 0° C. for 30 minutes
  5. filtrationThe solids were filtered
  6. washrinsed with ethyl acetate
  7. customLight yellow solids were further dried in a vacuum oven

Sources & evidence

ORD record
ord-fb4bad3aa9d9422f999f31e1b7562299
Source dataset
uspto-grants-2009_09
Patent number
US07585869B2

Reaction notes

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