Sodium Iodide → (S)-2-{[2-(2-1H-Indazol-4-yl-acetylamino)-4-methyl-thiazole-5-carbonyl]-amino}-3-[(thiophene-2-carbonyl)-amino]-propionic acid 1-(2,2-dimethyl-propionyloxy)-ethyl ester

HRID 1952662ノート

反応式

HRID 1952662 の反応式
[NH:1]1[C:9]2[C:4](=[C:5]([CH2:10][C:11]([NH:13][C:14]3[S:15][C:16]([C:20]([NH:22][C@@H:23]([CH2:27][NH:28][C:29]([C:31]4[S:32][CH:33]=[CH:34][CH:35]=4)=[O:30])[C:24]([OH:26])=[O:25])=[O:21])=[C:17]([CH3:19])[N:18]=3)=[O:12])[CH:6]=[CH:7][CH:8]=2)[CH:3]=[N:2]1.Cl[CH:37]([O:39][C:40](=[O:45])[C:41]([CH3:44])([CH3:43])[CH3:42])[CH3:38].C(N(CC)CC)C.[I-].[Na+]>CN(C=O)C>[CH3:42][C:41]([CH3:44])([CH3:43])[C:40]([O:39][CH:37]([O:25][C:24](=[O:26])[C@@H:23]([NH:22][C:20]([C:16]1[S:15][C:14]([NH:13][C:11](=[O:12])[CH2:10][C:5]2[CH:6]=[CH:7][CH:8]=[C:9]3[C:4]=2[CH:3]=[N:2][NH:1]3)=[N:18][C:17]=1[CH3:19])=[O:21])[CH2:27][NH:28][C:29]([C:31]1[S:32][CH:33]=[CH:34][CH:35]=1)=[O:30])[CH3:38])=[O:45]

参加物

6

反応物 4

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 30161741-Chloroethyl pivalateHCID 51035164(S)-2-{[2-(2-1H-Indazol-4-yl-acetylamino)-4-methyl-thiazole-5-carbonyl]-amino}-3-[(thiophene-2-carbonyl)-amino]-propionic acid

生成物 1

HCID 60202694(S)-2-{[2-(2-1H-Indazol-4-yl-acetylamino)-4-methyl-thiazole-5-carbonyl]-amino}-3-[(thiophene-2-carbonyl)-amino]-propionic acid 1-(2,2-dimethyl-propionyloxy)-ethyl ester

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A solution of (S)-2-{[2-(2-1H-Indazol-4-yl-acetylamino)-4-methyl-thiazole-5-carbonyl]-amino}-3-[(thiophene-2-carbonyl)-amino]-propionic acid (70.2 mg, 0.137 mmol), 2,2-Dimethyl-propionic acid 1-chloro-ethyl ester (51 mg, 0.310 mmol), triethylamine (22 mg, 0.217 mmol) and sodium iodide (15 mg, 0.10 mmol) in anhydrous DMF (2.5 mL) was microwaved at 150° C. for 10 min and then concentrated at reduced pressure to remove most of the DMF. The residue was diluted with ethyl acetate (40 mL), washed with water (10 mL), brine (10 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The resulting crude compound was purified by flash chromatography (50% to 80% EtOAc in hexanes) to give(S)-2-{[2-(2-1H-Indazol-4-yl-acetylamino)-4-methyl-thiazole-5-carbonyl]-amino}-3-[(thiophene-2-carbonyl)-amino]-propionic acid 1-(2,2-dimethyl-propionyloxy)-ethyl ester (25.4 mg, 28.9%) as a yellow solid. MS m/e 641.7 (M+H+).

後処理

  1. concentrationconcentrated at reduced pressure
  2. customto remove most of the DMF
  3. additionThe residue was diluted with ethyl acetate (40 mL)
  4. washwashed with water (10 mL), brine (10 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting crude compound was purified by flash chromatography (50% to 80% EtOAc in hexanes) to give(S)-2-{[2-(2-1H-Indazol-4-yl-acetylamino)-4-methyl-thiazole-5-carbonyl]-amino}-3-[(thiophene-2-carbonyl)-amino]-propionic acid 1-(2,2-dimethyl-propionyloxy)-ethyl ester (25.4 mg, 28.9%) as a yellow solid

出典と根拠

ORDレコード
ord-a3eff3a502064b2aa2e5ec956364a93c
出典データセット
uspto-grants-2013_03
特許番号
US08404859B2

反応ノート

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