Diisopropylethylamine → 2-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(p-tolylethynyl)-1,2,4-oxadiazol-3-yl)benzyl)benzamido)acetic acid

HRID 923611ノート

反応式

HRID 923611 の反応式
[OH:1][NH:2][C:3]([C:5]1[CH:44]=[CH:43][C:8]([CH2:9][N:10]([CH2:35][C:36]([O:38]C(C)(C)C)=[O:37])[C:11](=[O:34])[C:12]2[CH:17]=[CH:16][C:15]([NH:18][C:19](=[O:33])[CH2:20][C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][C:22]=3[C:29]([F:32])([F:31])[F:30])=[CH:14][CH:13]=2)=[CH:7][CH:6]=1)=[NH:4].CCN(C(C)C)C(C)C.[C:54]1([CH3:65])[CH:59]=[CH:58][C:57]([C:60]#[C:61][C:62](Cl)=O)=[CH:56][CH:55]=1>CC(=O)OCC>[CH3:28][O:27][C:24]1[CH:25]=[CH:26][C:21]([CH2:20][C:19]([NH:18][C:15]2[CH:16]=[CH:17][C:12]([C:11]([N:10]([CH2:35][C:36]([OH:38])=[O:37])[CH2:9][C:8]3[CH:43]=[CH:44][C:5]([C:3]4[N:4]=[C:62]([C:61]#[C:60][C:57]5[CH:58]=[CH:59][C:54]([CH3:65])=[CH:55][CH:56]=5)[O:1][N:2]=4)=[CH:6][CH:7]=3)=[O:34])=[CH:13][CH:14]=2)=[O:33])=[C:22]([C:29]([F:32])([F:31])[F:30])[CH:23]=1

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 146651233-(4-Methylphenyl)prop-2-ynoyl chlorideHCID 178490478HCID 178490478、化合物

生成物 1

HCID 710784202-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(p-tolylethynyl)-1,2,4-oxadiazol-3-yl)benzyl)benzamido)acetic acid収率 19%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

Prepared using General Procedures 20 and 8. To a stirred solution of tert-butyl 2-(N-(4-(N-hydroxycarbamimidoyl)benzyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)acetate INT-33 (200 mg, 0.325 mmol) in dioxanes (4 mL) was added DIEA (85 μL, 0.488 mmol) then 3-(p-tolyl)propioloyl chloride (60 mg, 0.36 mmol). The reaction mixture was stirred at room temperature for 30 mins then at 120° C. for 3 h. The reaction mixture was allowed to cool to room temperature, diluted with EA (100 mL) and washed with brine (100 mL). The organics were concentrated and the residue diluted with DCM (5 mL) and TFA (2 mL) was added. The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was concentrated in vacuo and purified by preparative HPLC to afford 44 mg (19%) of 2-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(p-tolylethynyl)-1,2,4-oxadiazol-3-yl)benzyl)benzamido)acetic acid 471 as an off-white powder. LCMS-ESI (m/z) calculated for C37H29F3N4O6: 682; found 683 [M+H]+, tR=8.49 min (Method 9).

後処理

  1. customPrepared
  2. waitat 120° C. for 3 h
  3. temperatureto cool to room temperature
  4. washwashed with brine (100 mL)
  5. concentrationThe organics were concentrated
  6. additionthe residue diluted with DCM (5 mL) and TFA (2 mL)
  7. additionwas added
  8. stirringThe reaction mixture was stirred at room temperature for 2 h
  9. concentrationThe reaction mixture was concentrated in vacuo
  10. custompurified by preparative HPLC

出典と根拠

ORDレコード
ord-c603026ca4f348468010ee0566f7a9a4
出典データセット
uspto-grants-2016_03
特許番号
US09278910B2

反応ノート

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