Triethylamine → HCID 57970155, compound

HRID 1666644Notes

Reaction equation

HRID 1666644 reaction equation
NN1CCCC1.Cl[C:8]1[N:17]=[C:16]([O:18][CH3:19])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[N:9]=1.Cl.[NH2:21][C@H:22]1[CH2:26][CH2:25][N:24]([C:27](=[O:40])[CH2:28][C:29]2[CH:34]=[CH:33][C:32]([O:35][C:36]([F:39])([F:38])[F:37])=[CH:31][CH:30]=2)[CH2:23]1.C(N(CC)CC)C>C(Cl)(Cl)Cl.C1COCC1>[CH3:19][O:18][C:16]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[N:9]=[C:8]([NH:21][C@H:22]2[CH2:26][CH2:25][N:24]([C:27](=[O:40])[CH2:28][C:29]3[CH:30]=[CH:31][C:32]([O:35][C:36]([F:37])([F:38])[F:39])=[CH:33][CH:34]=3)[CH2:23]2)[N:17]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 279461-PyrrolidinamineHCID 126843412-Chloro-4-methoxyquinazolineHCID 86636479(S)-1-(3-aminopyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone mono hydrochloride

Product 1

HCID 57970155HCID 57970155, compoundYield 6.5%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

Metal sodium (35 mg) was added to methanol (1.5 mL) to prepare a solution, and the solution was concentrated under reduced pressure, followed by addition of THF (1.5 mL). This suspension was added to a solution of 2,4-dichloroquinazoline (0.30 g) in THF (1.5 mL), and the mixture was stirred at room temperature for 2 h. To the reaction mixture was added saturated brine, the mixture was extracted with chloroform, and the organic layer was dried with anhydrous magnesium sulfate. The desiccant was removed by filtration, the filtrate was concentrated under reduced pressure, and then the residue was purified by silica gel column chromatography (hexane/ethyl acetate=9:1) to obtain 2-chloro-4-methoxyquinazoline (0.27 g). (2) A mixture of 2-chloro-4-methoxyquinazoline (0.25 g), 1-((S)-3-aminopyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone mono hydrochloride (0.42 g), triethylamine (0.33 g), and THF (3.2 mL) was heated at 100° C. in a microwave reaction apparatus for 3 h. The reaction mixture was diluted with chloroform, washed with 1 M aqueous sodium hydroxide, and then dried with anhydrous magnesium sulfate. The desiccant was removed by filtration, the filtrate was concentrated under reduced pressure, and then the residue was purified by silica gel column chromatography (chloroform-chloroform/methanol=95:5, and silica gel, hexane/ethyl acetate=1:2−ethyl acetate) to obtain the title compound (37 mg).

Workup

  1. washwashed with 1 M aqueous sodium hydroxide
  2. dry with materialdried with anhydrous magnesium sulfate
  3. customThe desiccant was removed by filtration
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (chloroform-chloroform/methanol=95:5, and silica gel, hexane/ethyl acetate=1:2−ethyl acetate)

Sources & evidence

ORD record
ord-3157e99087214b2096f80ea5f96d090b
Source dataset
uspto-grants-2011_10
Patent number
US08044068B2

Reaction notes

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