Diisopropylethylamine → 6-Chloro-2-(3,3-difluoro-azetidin-1-yl)-quinoline-5-carboxylic acid (4,4-difluoro-cyclohexylmethyl)-amide

HRID 1056665Notes

Reaction equation

HRID 1056665 reaction equation
[F:1][C:2]1([F:24])[CH2:7][CH2:6][CH:5]([CH2:8][NH:9][C:10]([C:12]2[C:13]3[CH:14]=[CH:15][C:16](Cl)=[N:17][C:18]=3[CH:19]=[CH:20][C:21]=2[Cl:22])=[O:11])[CH2:4][CH2:3]1.Cl.[F:26][C:27]1([F:31])[CH2:30][NH:29][CH2:28]1.CCN(C(C)C)C(C)C>C(#N)C>[F:1][C:2]1([F:24])[CH2:7][CH2:6][CH:5]([CH2:8][NH:9][C:10]([C:12]2[C:13]3[CH:14]=[CH:15][C:16]([N:29]4[CH2:30][C:27]([F:31])([F:26])[CH2:28]4)=[N:17][C:18]=3[CH:19]=[CH:20][C:21]=2[Cl:22])=[O:11])[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27582473,3-Difluoroazetidine hydrochlorideHCID 1185559652,6-Dichloro-quinoline-5-carboxylic acid (4,4-difluorocyclohexylmethyl)-amide

Product 1

HCID 1185666126-Chloro-2-(3,3-difluoro-azetidin-1-yl)-quinoline-5-carboxylic acid (4,4-difluoro-cyclohexylmethyl)-amideYield 59%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

In a microwave vial 2,6-dichloro-quinoline-5-carboxylic acid (4,4-difluoro-cyclohexylmethyl)-amide (100 mg, 0.27 mmol), 3,3-difluoro-azetidine hydrochloride (347.07 mg, 2.68 mmol) and DIPEA (519.43 mg, 4.02 mmol) in ACN (1.5 mL) was heated at 120° C. for 2 hours under microwave irradiation. After cooling to room temperature, the mixture was concentrated and purified through reverse phase HPLC to provide the desired product (68 mg, 59%) as a solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.75 (1H), 7.88 (1H), 6.69 (1H), 4.54 (4H), 3.24 (t, J=6.24 Hz, 2H), 2.04 (m, 2H), 1.85 (m, 2H), 1.74-1.76 (m, 3H), 1.27-1.30 (m, 2H). m/z: 430 [M+H]

Workup

  1. concentrationthe mixture was concentrated
  2. custompurified through reverse phase HPLC

Sources & evidence

ORD record
ord-da4d8d81729e47c28e0decf9fd2c1f2f
Source dataset
uspto-grants-2016_07
Patent number
US09399623B2

Reaction notes

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