2-(4-Bromo-2-fluorophenylamino)-6-formylaminomethylnicotinic acid methyl ester → 5-(4-Bromo-2-fluorophenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid methyl ester

HRID 1500681ノート

反応式

HRID 1500681 の反応式
[CH3:1][O:2][C:3](=[O:23])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][NH:11][CH:12]=O)=[N:6][C:5]=1[NH:14][C:15]1[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=1[F:22].O(Cl)Cl.[P+5]>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]([C:4]1[CH:9]=[CH:8][C:7]2[N:6]([CH:12]=[N:11][CH:10]=2)[C:5]=1[NH:14][C:15]1[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=1[F:22])=[O:23]

参加物

4

反応物 2

HCID 591401622-(4-Bromo-2-fluorophenylamino)-6-formylaminomethylnicotinic acid methyl esterHCID 178479711HCID 178479711、化合物

生成物 1

HCID 591401535-(4-Bromo-2-fluorophenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid methyl ester収率 49%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
95 °C

実験手順

To a solution of 2-(4-Bromo-2-fluorophenylamino)-6-formylaminomethylnicotinic acid methyl ester (11.8 g, 30.9 mmol) in toluene (550 mL) was added phosphorous (V) oxychloride (3.16 mL, 34 mmol) and the reaction mixture heated at 95° C. for 1 hour. The reaction mixture was concentrated in vacuo and treated with aqueous saturated sodium hydrogen carbonate solution then extracted twice with ethyl acetate. The combined organic fractions were washed with brine, dried (Na2SO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si-PPC, gradient 0-30% ethyl acetate in DCM) to yield the title compound as a brown oil (5.4 g, 49%). LCMS (Method B): RT=3.56 min, M+H+=364/366.

後処理

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additiontreated with aqueous saturated sodium hydrogen carbonate solution
  3. extractionthen extracted twice with ethyl acetate
  4. washThe combined organic fractions were washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-8762685b39e5427c876f4711fd08e141
出典データセット
uspto-grants-2015_12
特許番号
US09206174B2

反応ノート

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