Toluene → N-(2-methyl-2H-indazol-6-yl)-2-{[2-(3-methyl-ureido)-pyridin-4-ylmethyl]-amino}-nicotinamide

HRID 602417ノート

反応式

HRID 602417 の反応式
[CH3:1][N:2]1[CH:10]=[C:9]2[C:4]([CH:5]=[C:6]([NH2:11])[CH:7]=[CH:8]2)=[N:3]1.C[Al](C)C.C1(C)C=CC=CC=1.C[O:24][C:25](=O)[C:26]1[CH:31]=[CH:30][CH:29]=[N:28][C:27]=1[NH:32][CH2:33][C:34]1[CH:39]=[CH:38][N:37]=[C:36]([NH:40][C:41]([NH:43][CH3:44])=[O:42])[CH:35]=1.C(C(C(C([O-])=O)O)O)([O-])=O.[K+].[Na+]>ClCCCl>[CH3:1][N:2]1[CH:10]=[C:9]2[C:4]([CH:5]=[C:6]([NH:11][C:25](=[O:24])[C:26]3[CH:31]=[CH:30][CH:29]=[N:28][C:27]=3[NH:32][CH2:33][C:34]3[CH:39]=[CH:38][N:37]=[C:36]([NH:40][C:41]([NH:43][CH3:44])=[O:42])[CH:35]=3)[CH:7]=[CH:8]2)=[N:3]1

参加物

7

反応物 5

HCID 1140TolueneHCID 5902202-Methyl-2H-indazol-6-amineHCID 9855836Potassium sodium tartarateHCID 16682925TrimethylaluminumHCID 586749452-{[2-(3-Methyl-ureido)-pyridin-4-ylmethyl]-amino}-nicotinic acid methyl ester

生成物 1

HCID 11611709N-(2-methyl-2H-indazol-6-yl)-2-{[2-(3-methyl-ureido)-pyridin-4-ylmethyl]-amino}-nicotinamide収率 53%

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒2 回

反応条件

温度
85 °C

実験手順

A suspension of 2-methyl-2H-indazol-6-ylamine [Davies J. Chem. Soc.; 1955; 2412-2419] (809 mg, 5.5 mmol) in DCE (13.5 mL) was treated at 0° C. consecutively with, trimethylaluminium (2 M) in toluene (4.23 mL, 8.46 mmol), 2-{[2-(3-methyl-ureido)-pyridin-4-ylmethyl]-amino}-nicotinic acid methyl ester (1.34 g, 4.23 mmol) and DCE (20 mL). The reaction mixture was placed under a nitrogen atmosphere and heated for 10 hours at 85° C. (bath temperature). On cooling the reaction was poured into aqueous sodium-potassium tartrate solution (150 mL) and partitioned between EtOAc and water. The organic phase was washed with brine, dried, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel (Gradient elution: 100% CH2Cl2 to 90% CH2Cl2/10% MeOH) to give N-(2-methyl-2H-indazol-6-yl)-2-{[2-(3-methyl-ureido)-pyridin-4-ylmethyl]-amino}-nicotinamide (964 mg, 53%) as a solid; Mp. 205-207° C.

後処理

  1. temperatureOn cooling the reaction
  2. custompartitioned between EtOAc and water
  3. washThe organic phase was washed with brine
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by chromatography on silica gel (Gradient elution: 100% CH2Cl2 to 90% CH2Cl2/10% MeOH)

出典と根拠

ORDレコード
ord-d2ef29d827fd4511b2b807b41a627d4d
出典データセット
uspto-grants-2011_03
特許番号
US07906533B2

反応ノート

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