Chloroacetyl chloride → HCID 89096210, compound

HRID 2277425Notes

Reaction equation

HRID 2277425 reaction equation
Cl.[NH:2]1[CH2:5][CH:4]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[C:9](=[O:25])[C:8]=2[C:26]#[N:27])[CH2:3]1.[Cl:28][CH2:29][C:30](Cl)=[O:31].CCN(C(C)C)C(C)C>ClCCl>[Cl:28][CH2:29][C:30]([N:2]1[CH2:5][CH:4]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]([CH2:17][C:18]3[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=3)[C:9](=[O:25])[C:8]=2[C:26]#[N:27])[CH2:3]1)=[O:31]

Participants

5

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 81531DiisopropylethylamineHCID 117925565HCID 117925565, compound

Product 1

HCID 89096210HCID 89096210, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-10 °C

Procedure

To a suspension of 4-(Azetidin-3-ylamino)-1-(4-fluoro-benzyl)-2-oxo-1,2-dihydro-quinoline-3-carbonitrile hydrochloride salt (1 eq, 0.150 g, 0.43 mmole) in dichloromethane at −10° C. was added chloroacetyl chloride (1.1 eq, 0.054 g, 0.474 mmole) followed by the addition of N,N′-diisopropylethylamine (1.5 eq, 0.083 g, 0.646 mmole, 0.110 mL). The resulting solution stirred at −10° C. for 1 hour then warmed to RT and stirred for an additional 2 hours. The reaction was quenched into ice cooled water and extracted with ethyl acetate (25 mL×3). Combined organic phase was washed consecutively with water, brine before drying over sodium sulfate. Organic phase was evaporated and the residue was purified by flash chromatography to afford 4-[1-(2-Chloro-acetyl)-azetidin-3-ylamino]-1-(4-fluoro-benzyl)-2-oxo-1,2-dihydro-quinoline-3-carbonitrile as a yellow solid (0.027 g, 15% calc M+H 425, obs M+H 425).

Workup

  1. temperaturethen warmed to RT
  2. stirringstirred for an additional 2 hours
  3. customThe reaction was quenched into ice
  4. temperaturecooled water
  5. extractionextracted with ethyl acetate (25 mL×3)
  6. washCombined organic phase was washed consecutively with water, brine
  7. dry with materialbefore drying over sodium sulfate
  8. customOrganic phase was evaporated
  9. customthe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-3d7d79e625964e08af2a8a0e8842f85c
Source dataset
uspto-grants-2015_09
Patent number
US09133164B2

Reaction notes

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