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

HRID 1398306노트

반응식

HRID 1398306 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.C1(N)CC1>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]3[CH2:27][CH2:25]3)=[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 69828CyclopropylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 866959074-(4-Chloro-2-fluorophenyl)nicotinic acid

생성물 1

HCID 867103144-(4-chloro-2-fluorophenyl)-N-cyclopropylnicotinamide수율 83%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of 4-(4-chloro-2-fluorophenyl)nicotinic acid (500 mg, 1.987 mmol) (prepared as in Ex. 2, Part A) in DMF (6 mL) cooled to 0° C. was added EDC (571 mg, 2.98 mmol) and HOBT (609 mg, 3.97 mmol) and the mixture was stirred for 5 min. To the resultant solution DIPEA (1.04 mL, 5.96 mmol) followed by cyclopropanamine (567 mg, 9.93 mmol) was 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-cyclopropylnicotinamide (480 mg, 1.65 mmol, 83% yield). LC/MS (ESI) m/e 291.0 [(M+H)+, calcd for C15H13ClFN2O 291.1]; LC/MS retention time (method C): tR=1.79 min.

후처리

  1. additionwas 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-c34a75d0de4e42228f16e5e61b9469fb
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08901305B2

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