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2-Chloronicotinic acid → 2-Chloro-N-[1-(2,6-dichloro-pyridin-3-yl)-cyclopropylmethyl]nicotinamide

HRID 578877
ノート
印刷プレビュー

反応式

HRID 578877 の反応式
[Cl:1][C:2]1[C:7]([C:8]2([CH2:11][NH2:12])[CH2:10][CH2:9]2)=[CH:6][CH:5]=[C:4]([Cl:13])[N:3]=1.FC(F)(F)C1C(C(O)=O)=NC=CC=1.CCN=C=NCCCN(C)C.Cl.C1C=C2N=NN(O)C2=CC=1.O.[Cl:50][C:51]1[C:56]([C:57](O)=[O:58])=[CH:55][CH:54]=[CH:53][N:52]=1>ClCCl.O.C(N(CC)CC)C>[Cl:50][C:51]1[N:52]=[CH:53][CH:54]=[CH:55][C:56]=1[C:57]([NH:12][CH2:11][C:8]1([C:7]2[C:2]([Cl:1])=[N:3][C:4]([Cl:13])=[CH:5][CH:6]=2)[CH2:9][CH2:10]1)=[O:58]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

9

反応物 5

HCID 762582-Chloronicotinic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 132338443-(Trifluoromethyl)pyridine-2-carboxylic acidHCID 89544422[1-(2,6-Dichloropyridin-3-yl)cyclopropyl]methanamine

生成物 1

HCID 71558841
2-Chloro-N-[1-(2,6-dichloro-pyridin-3-yl)-cyclopropylmethyl]nicotinamide

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 8471Triethylamine溶媒

反応条件

温度
0 °C

実験手順

0.45 ml of C-[1-(2,6-dichloro-pyridin-3-yl)-cyclopropyl]-methylamine was dissolved in 1.5 ml of dichloromethane under argon and 0.11 ml of triethylamine was added at ambient temperature. Ther reaction mixture was cooled at 0° C. and 383 mg of 3-(trifluoromethyl)pyridine-2-carboxylic acid, 145 mg of EDCI.HCl, 103 mg of HOBT hydrate and 59 mg of 2-chloropyridine-3-carboxylic acid were added sequentially. The reaction mixture was stirred at ambient temperature for 14 hours. Then water was added, the phases were separated and the aqueous phase was extracted with dichloromethane. The organic layers were combined, dried with anhydrous sodium sulphate, filtered and concentrated. Crude material was obtained as a yellow sticky solid, which was purified by trituration in diethyl ether to give 60 mg of the desired 2-Chloro-N-[1-(2,6-dichloro-pyridin-3-yl)-cyclopropylmethyl]nicotinamide as white solid. 1H-NMR (CDCl3): 8.45 ppm (m, 1H), 8.04 ppm (m, 1H), 7.68 ppm (d, 1H), 7.34 ppm (m, 1H), 6.53 ppm (m, 1H), 3.72 ppm (d, 2H), 1.19 ppm (m, 2H), 0.96 ppm (m, 2H).

後処理

  1. customthe phases were separated
  2. extractionthe aqueous phase was extracted with dichloromethane
  3. dry with materialdried with anhydrous sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customCrude material was obtained as a yellow sticky solid, which
  7. customwas purified by trituration in diethyl ether

出典と根拠

ORDレコード
ord-7b8187907c6e474389e188ea231719e9
出典データセット
uspto-grants-2015_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09040708B2

反応ノート

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