Triethylamine → HCID 11293770, compound

HRID 731899Notes

Reaction equation

HRID 731899 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[N:10]=[CH:9][N:8]=[C:7]2[NH:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)=[C:17]([CH3:28])[CH:16]=1.C(N(CC)CC)C.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH:48]1([CH2:51][C:52](O)=[O:53])[CH2:50][CH2:49]1>CN(C)C=O>[CH:48]1([CH2:51][C:52]([N:25]2[CH2:26][CH2:27][CH:22]([O:21][C:18]3[CH:19]=[CH:20][C:15]([NH:14][C:7]4[C:6]5[C:11](=[CH:12][CH:13]=[C:4]([O:3][CH3:2])[CH:5]=5)[N:10]=[CH:9][N:8]=4)=[CH:16][C:17]=3[CH3:28])[CH2:23][CH2:24]2)=[O:53])[CH2:50][CH2:49]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 138440Cyclopropaneacetic acidHCID 69052599HCID 69052599, compound

Product 1

HCID 11293770HCID 11293770, compoundYield 63.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of (6-Methoxy-quinazolin-4-yl)-[3-methyl-4-(piperidin-4-yloxy)-phenyl]-amine hydrochloride (108mg, 0.251 mmol) in N,N-dimethylformamide (1.0 mL) was added triethylamine (143 μL, 1.03 mmol) and the preformed acyl imidazolide (0.343 mmol). The acyl imidazolide is prepared by mixing CDI (56 mg, 0.343 mmol), DMF (1 mL) and cyclopropylacetic acid (34 mg, 0.343 mmol) and stirring for one hour at ambient temperature. After addition of the acyl imidzolide, the reaction was stirred at room temperature overnight. The reaction was then filtered through a 0.45 μm PTFE membrane filter and purified by preparatory HPLC. 71.4 mg of 2-Cyclopropyl-1-{4-[4-(6-methoxy-quinazolin-4-ylamino)-2-methyl-phenoxy]-piperidin-1-yl}-ethanone was isolated. 1H NMR (300 MHz DMSO d6), δ 9.505 (s, 1H), 8.435 (s, 1H) 7.904 (d, J=9.0, 2.7 Hz, 1H), 7.708 (d, J=9.0 Hz, 1H), 7.552 (dd, J=2.7 Hz, 1H), 7.576-7.511 (m, 2H), 7.480 (dd, J=9.0, 2.7 Hz, 1H), 7.062 (d, J=9.0 Hz, 1H), 4.647-4.600 (m, 1H), 3.951 (s, 3H), 3.951-3.730 (m, 1H), (m, 1H), 3.729-3.645 (m, 1H), 3.442-3.369 (m, 3H), 2.300 (d, J=6.9 Hz, 2H), 2.223 (s, 1H), 1.985-1.882 (m, 2H), 1.692-1.576 (m, 2H) 0.980 (m, 1H), 0.499-0.439 (m, 2H), 0.162-0.113 (m, 2H).

Workup

  1. stirringthe reaction was stirred at room temperature overnight
  2. filtrationThe reaction was then filtered through a 0.45 μm PTFE membrane
  3. filtrationfilter
  4. custompurified by preparatory HPLC

Sources & evidence

ORD record
ord-f0f0709a20ad48079a5314f4e7095e88
Source dataset
uspto-grants-2009_09
Patent number
US07585869B2

Reaction notes

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