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

HRID 1398306ノート

反応式

HRID 1398306 の反応式
[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

参加物

7

反応物 5

HCID 111,2-DichloroethaneHCID 69828CyclopropylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 866959074-(4-Chloro-2-fluorophenyl)nicotinic acid

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-c34a75d0de4e42228f16e5e61b9469fb
出典データセット
uspto-grants-2014_12
特許番号
US08901305B2

反応ノート

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