Triethylamine → HCID 57639703、化合物

HRID 909200ノート

反応式

HRID 909200 の反応式
[F:1][C:2]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:3]=1[O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:13]=1[C:14](O)=[O:15])[N:10]([CH2:17][CH:18]([CH3:20])[CH3:19])[N:9]=[CH:8]2.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[NH2:49][C@@H:50]([CH2:55][CH2:56][N:57]([CH3:59])[CH3:58])[C:51]([O:53][CH3:54])=[O:52].C(N(CC)CC)C>ClC(Cl)C.ClCCl>[F:1][C:2]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:3]=1[O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:13]=1[C:14]([NH:49][C@@H:50]([CH2:55][CH2:56][N:57]([CH3:59])[CH3:58])[C:51]([O:53][CH3:54])=[O:52])=[O:15])[N:10]([CH2:17][CH:18]([CH3:20])[CH3:19])[N:9]=[CH:8]2

参加物

8

反応物 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 574187635-(2,4-Difluorophenoxy)-1-isobutyl-1H-indazole-6-carboxylic acidHCID 86594424HCID 86594424、化合物

生成物 1

HCID 57639703HCID 57639703、化合物収率 71%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 63651,1-Dichloroethane溶媒

実験手順

5-(2,4-Difluorophenoxy)-1-isobutyl-1H-indazole-6-carboxylic acid (17d; prepared according to Example 110) (0.396 g, 1.14 mmol) was stirred with HOBt (0.192 g, 1.26 mmol) and EDCI (0.241 g, 1.26 mmol) in dichloroethane (2 mL) for 10 minutes at room temperature. This mixture was then added to a suspension of (S)-methyl 2-amino-4-(dimethylamino)butanoate dihydrochloride (0.280 g, 1.20 mmol) and triethylamine (1 mL, 6.9 mmol) in dichloromethane (6 mL). The reaction mixture was stirred for 3 hours and then was concentrated under reduced pressure. The residue was diluted with chloroform (50 mL) and washed with 1N HCl (2×25 mL), saturated K2CO3 (2×50 mL), water (25 mL), brine (25 mL), and dried over MgSO4. The filtered solution was concentrated under reduced pressure to provide yellow oil. The oil was chromatographed eluting with 5% MeOH in dichloromethane to afford a viscous colorless oil that solidified upon drying under high vacuum (0.393 g, 71% yield). MS (ESI+) m/z 489 (M+1) detected; 1H NMR (400 mHz, CDCl3) δ 8.91 (d, 1H), 8.36 (s, 1H), 7.86 (s, 1H), 7.16 (m, 1H), 7.03 (m, 1H), 7.00 (s, 1H), 6.93 (m, 1H), 4.88 (m, 1H), 4.21 (d, 2H), 3.74 (s, 3H), 2.34 (m, 3H), 2.06 (s, 6H), 2.01 (m, 2H), 0.92 (d, 6H).

後処理

  1. concentrationwas concentrated under reduced pressure
  2. additionThe residue was diluted with chloroform (50 mL)
  3. washwashed with 1N HCl (2×25 mL), saturated K2CO3 (2×50 mL), water (25 mL), brine (25 mL)
  4. dry with materialdried over MgSO4
  5. concentrationThe filtered solution was concentrated under reduced pressure
  6. customto provide yellow oil
  7. customThe oil was chromatographed
  8. washeluting with 5% MeOH in dichloromethane
  9. customto afford a viscous colorless oil that
  10. customupon drying under high vacuum (0.393 g, 71% yield)

出典と根拠

ORDレコード
ord-2efe4f5c46474d90b52038ff5b927aef
出典データセット
uspto-grants-2011_09
特許番号
US08017641B2

反応ノート

読み込み中…