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

HRID 1398302ノート

反応式

HRID 1398302 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.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

参加物

7

反応物 5

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

生成物 1

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

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 (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.

後処理

  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

出典と根拠

ORDレコード
ord-d5d1af31ef5f43279a09dacc66a18b31
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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