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Formaldehyde → 1-[(3-{2-[3-Cyano-4-(2-methylpropyl)phenyl]-1,3-thiazol-5-yl}-2-ethylphenyl)methyl]-3-azetidinecarboxylic acid

HRID 1942748
ノート
印刷プレビュー

反応式

HRID 1942748 の反応式
[CH2:1]([C:3]1[C:8]([CH:9]=O)=[CH:7][CH:6]=[CH:5][C:4]=1[C:11]1[S:15][C:14]([C:16]2[CH:17]=[CH:18][C:19]([CH2:24][CH:25]([CH3:27])[CH3:26])=[C:20]([CH:23]=2)[C:21]#[N:22])=[N:13][CH:12]=1)[CH3:2].[NH:28]1[CH2:31][CH:30]([C:32]([OH:34])=[O:33])[CH2:29]1.C([BH3-])#N.[Na+].C=O>C(O)C.C(O)(=O)C>[C:21]([C:20]1[CH:23]=[C:16]([C:14]2[S:15][C:11]([C:4]3[C:3]([CH2:1][CH3:2])=[C:8]([CH2:9][N:28]4[CH2:31][CH:30]([C:32]([OH:34])=[O:33])[CH2:29]4)[CH:7]=[CH:6][CH:5]=3)=[CH:12][N:13]=2)[CH:17]=[CH:18][C:19]=1[CH2:24][CH:25]([CH3:27])[CH3:26])#[N:22]
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 712FormaldehydeHCID 931923-azetidinecarboxylic AcidHCID 5003444Sodium cyanoborohydrideHCID 866590095-[5-(2-Ethyl-3-formylphenyl)-1,3-thiazol-2-yl]-2-(2-methylpropyl)benzonitrile

生成物 1

HCID 545771591-[(3-{2-[3-Cyano-4-(2-methylpropyl)phenyl]-1,3-thiazol-5-yl}-2-ethylphenyl)methyl]-3-azetidinecarboxylic acid収率 21.7%

試薬・触媒・溶媒

2
HCID 176Acetic Acid溶媒HCID 702Ethanol溶媒

実験手順

A solution of 5-[5-(2-ethyl-3-formylphenyl)-1,3-thiazol-2-yl]-2-(2-methylpropyl)benzonitrile (D92) (120 mg), 3-azetidinecarboxylic acid (64.8 mg) and acetic acid (0.1 mL) in ethanol (10 mL) was stirred at room temperature for 15 min, then sodium cyanoborohydride (60.4 mg) was added. The mixture was stirred at room temperature for 6 h, then formaldehyde (0.11 mL) was added. The mixture was stirred at room temperature overnight. After concentration, the residue was acidified with 2M HCl to pH 5-6, ethyl acetate was added, the organic phase was washed with saturated brine, then dried and evaporated. The residue was purified by Mass Directed AutoPrep to afford 1-[(3-{2-[3-cyano-4-(2-methylpropyl)phenyl]-1,3-thiazol-5-yl}-2-ethylphenyl)methyl]-3-azetidinecarboxylic acid (E43) (32 mg) as a TFA salt. δH (DMSO-d6, 400 MHz): 0.92 (6H, d), 1.05 (3H, t), 1.98 (1H, m), 2.76 (4H, m), 3.65 (1H, m), 4.27 (4H, m), 4.54 (2H, br. s.), 7.40 (1H, m), 7.48 (2H, m), 7.62 (1H, d), 7.94 (1H, s), 8.22 (1H, dd), 8.35 (1H, d), 10.21 (1H, br s), 13.19 (1H, br s). δF (DMSO-d6, 376 MHz): −73.5. MS (ES): C27H29N3O2S requires 459. found 460.2 (M+H+).

後処理

  1. stirringThe mixture was stirred at room temperature overnight
  2. concentrationAfter concentration
  3. additionwas added
  4. washthe organic phase was washed with saturated brine
  5. customdried
  6. customevaporated
  7. customThe residue was purified by Mass Directed AutoPrep

出典と根拠

ORDレコード
ord-b6a96d9815f544f4befd369fee107e0a
出典データセット
uspto-grants-2013_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08389508B2

反応ノート

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