Triethylamine → 4-(6,7-Dimethoxy-quinazolin-4-yl)-piperidine-1-carboxylic acid [4-(2-methoxy-ethoxy)-phenyl]-amide

HRID 657220

Reaction equation

HRID 657220 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[CH:15]1[CH2:20][CH2:19][N:18]([C:21](Cl)=[O:22])[CH2:17][CH2:16]1.[CH3:24][O:25][CH2:26][CH2:27][O:28][C:29]1[CH:34]=[CH:33][C:32]([NH2:35])=[CH:31][CH:30]=1.C(N(CC)CC)C>CS(C)=O>[CH3:24][O:25][CH2:26][CH2:27][O:28][C:29]1[CH:34]=[CH:33][C:32]([NH:35][C:21]([N:18]2[CH2:19][CH2:20][CH:15]([C:6]3[C:5]4[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=4)[N:9]=[CH:8][N:7]=3)[CH2:16][CH2:17]2)=[O:22])=[CH:31][CH:30]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 38798854-(2-Methoxyethoxy)anilineHCID 587707144-(6,7-Dimethoxy-quinazolin-4-yl)-piperidine-1-carbonyl chloride

Product 1

HCID 587706704-(6,7-Dimethoxy-quinazolin-4-yl)-piperidine-1-carboxylic acid [4-(2-methoxy-ethoxy)-phenyl]-amideYield 23%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A mixture of 4-(6,7-dimethoxy-quinazolin-4-yl)-piperidine-1-carbonyl chloride (18 mg, 0.0536 mmol), as prepared in Example 3a, 4-(2-methoxy-ethoxy)-phenylamine (8.9 mg, 0.0533 mmol), as prepared in the previous step, and triethylamine (14 μL, 0.1 mmol) was stirred in DMSO (0.5 mL) at 50° C. overnight. The reaction was then cooled to RT, partitioned between EtOAc (10 mL) and H2O (10 mL). The organic phase was dried over Na2SO4 and concentrated in vacuo. Purification by prep tlc (1:9 MeOH/DCM) afforded the title compound as a brown solid (5.7 mg, 23%). 1H NMR (300 MHz, CDCl3) δ 9.16 (s, 1H), 7.28-7.25 (m, 4H), 6.89 (m, 2H), 6.33 (br s, NH), 4.29-4.24 (m, 2H), 4.12-4.07 (m, 8H), 3.74 (m, 2H), 3.59 (m, 1H), 3.45 (s, 3H), 3.17 (m, 2H), 2.22-2.08 (m, 2H), 2.05-1.97 (m, 2H); LC/MS (ESI): calcd mass 466.2, found 467.4 [M+1]+.

Workup

  1. custompartitioned between EtOAc (10 mL) and H2O (10 mL)
  2. dry with materialThe organic phase was dried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customPurification by prep tlc (1:9 MeOH/DCM)

Sources & evidence

ORD record
ord-4a1a84b89ac74354b0a138fe0beb19f1
Source dataset
uspto-grants-2011_12
Patent number
US08071768B2

Linked notes

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