1,2-Dichloroethane → 4-(4-chloro-2-fluorophenyl)-N-isopropylnicotinamide

HRID 1398302노트

반응식

HRID 1398302 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]([OH:16])=O)=[CH:12][N:11]=[CH:10][CH:9]=2)=[C:4]([F:17])[CH:3]=1.C(Cl)CCl.C1C=C[C:25]2N(O)N=[N:28][C:26]=2[CH:27]=1.CCN(C(C)C)C(C)C.CC(N)C>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]([NH:28][CH:26]([CH3:27])[CH3:25])=[O:16])=[CH:12][N:11]=[CH:10][CH:9]=2)=[C:4]([F:17])[CH:3]=1

참가 물질

7

반응물 5

HCID 111,2-DichloroethaneHCID 6363IsopropylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 866959074-(4-Chloro-2-fluorophenyl)nicotinic acid

생성물 1

HCID 867103114-(4-chloro-2-fluorophenyl)-N-isopropylnicotinamide수율 103.1%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of 4-(4-chloro-2-fluorophenyl)nicotinic acid (400 mg, 1.590 mmol) (prepared as in Ex. 2, Part A) in DMF (6 mL) cooled to 0° C. was added EDC (457 mg, 2.384 mmol) and HOBT (487 mg, 3.18 mmol) and the mixture was stirred for 5 min. To the resultant solution DIPEA (0.83 mL, 4.77 mmol) followed by propan-2-amine (470 mg, 7.95 mmol) were added and the mixture was stirred at room temperature for 12 h. The reaction mixture was treated with ice and extracted with ethyl acetate (3×10 mL). The combined organic layers were washed with brine (1×10 mL), dried (Na2SO4) and concentrated under reduced pressure to afford 4-(4-chloro-2-fluorophenyl)-N-isopropylnicotinamide (480 mg, 1.64 mmol, 100%) as an off-white solid. LC/MS (ESI) m/e 293.2 [(M+H)+, calcd for C15H15ClFN2O 293.1]; LC/MS retention time (method C): tR=1.84 min.

후처리

  1. additionwere added
  2. stirringthe mixture was stirred at room temperature for 12 h
  3. additionThe reaction mixture was treated with ice
  4. extractionextracted with ethyl acetate (3×10 mL)
  5. washThe combined organic layers were washed with brine (1×10 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-d5d1af31ef5f43279a09dacc66a18b31
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08901305B2

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