Benzaldehyde → 1-[5-(Benzylidene-amino)-6-chloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester

HRID 408773ノート

反応式

HRID 408773 の反応式
[CH:1](=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:9]([O:11][C:12]([C:14]1[CH:15]=[N:16][N:17]([C:19]2[N:23]([CH2:24][O:25][CH2:26][CH2:27][O:28][CH3:29])[C:22]3[CH:30]=[C:31]([Cl:35])[C:32]([NH2:34])=[CH:33][C:21]=3[N:20]=2)[CH:18]=1)=[O:13])[CH3:10].NC1C(Cl)=CC2NC(N3C=C(C(O)=O)C=N3)=NC=2C=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1>[CH2:9]([O:11][C:12]([C:14]1[CH:15]=[N:16][N:17]([C:19]2[N:23]([CH2:24][O:25][CH2:26][CH2:27][O:28][CH3:29])[C:22]3[CH:30]=[C:31]([Cl:35])[C:32]([N:34]=[CH:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[CH:33][C:21]=3[N:20]=2)[CH:18]=1)=[O:13])[CH3:10]

参加物

6

反応物 4

HCID 240BenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 444790641-(5-Amino-6-chloro-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acidHCID 669373191-[5-Amino-6-chloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester

生成物 1

HCID 669371281-[5-(Benzylidene-amino)-6-chloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester収率 78.4%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
23 °C

実験手順

Benzaldehyde (93.0 mg, 0.876 mmol), 1-[5-amino-6-chloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester (Intermediate from Example 41, product from Step A) (0.300 g, 0.762 mmol), THF (3 mL), and 4 Å molecular sieves (0.910 g) were combined and stirred for 18 h at 23° C. Sodium triacetoxyborohydride (0.242 g, 1.14 mmol) was added and stirring was continued for 4 days. The reaction was quenched with saturated aqueous sodium bicarbonate (15 mL) and stirred with dichloromethane (25 mL). This mixture was filtered and the layers were separated. The aqueous layer was extracted with dichlormethane (2×25 mL) and the combined organic layers were washed with brine (20 mL), dried, filtered, and concentrated under reduced pressure. The residue was purified (FCC) (10-45% EtOAc/hexanes) to yield the titled compound (0.288 g, 78% yield) as a 4:3 mixture of regioisomers. The titled compound was not stable enough to obtain a mass spectrum. 1H NMR (400 MHz, CDCl3): 8.87 (s, 1H), 8.48 (s, 1H), 8.19 (s, 1H), 8.03-7.94 (m, 2H), 7.73 (s, 1H), 7.58-7.48 (m, 3H), 7.39 (s, 1H), 6.12 (s, 2H), 4.36 (q, J=7.1 Hz, 2H), 3.7-3.6 (m, 2H), 3.5-3.4 (m, 2H), 3.32 (s, 3H), 1.39 (t, J=7.1 Hz, 3H).

後処理

  1. stirringstirring
  2. waitwas continued for 4 days
  3. customThe reaction was quenched with saturated aqueous sodium bicarbonate (15 mL)
  4. stirringstirred with dichloromethane (25 mL)
  5. filtrationThis mixture was filtered
  6. customthe layers were separated
  7. extractionThe aqueous layer was extracted with dichlormethane (2×25 mL)
  8. washthe combined organic layers were washed with brine (20 mL)
  9. customdried
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified (FCC) (10-45% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-5f3f3a04f4f94853a010dd1d30ae3f56
出典データセット
uspto-grants-2014_06
特許番号
US08759345B2

反応ノート

読み込み中…