Lithium Hexamethyldisilazide → HCID 57513783、化合物

HRID 2368442ノート

反応式

HRID 2368442 の反応式
CO[C:3](=[O:21])[C:4]([CH3:20])([NH:6][C:7]([N:9]1[CH2:13][CH2:12][C@H:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:10]1)=[O:8])[CH3:5].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH2:32]([N:39]1[C:43]([C:44]2[CH:49]=[CH:48][C:47]([F:50])=[CH:46][CH:45]=2)=[N:42][C:41]([NH2:51])=[N:40]1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>C1COCC1>[CH2:32]([N:39]1[C:43]([C:44]2[CH:49]=[CH:48][C:47]([F:50])=[CH:46][CH:45]=2)=[N:42][C:41]([NH:51][C:3]([C:4]([NH:6][C:7]([N:9]2[CH2:13][CH2:12][C@H:11]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH2:10]2)=[O:8])([CH3:5])[CH3:20])=[O:21])=[N:40]1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

参加物

5

反応物 3

HCID 2733832Lithium Hexamethyldisilazide2 回HCID 57435373HCID 57435373、化合物HCID 57513844HCID 57513844、化合物

生成物 1

HCID 57513783HCID 57513783、化合物

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒4 回

実験手順

THF (3 mL) was added to a flask containing 2-methyl-2-[((R)-3-phenyl-pyrrolidine-1-carbonyl)-amino]-propionic acid methyl ester (100 mg, 0.344 mmol) at 0° C. under N2. In a dropwise fashion 1 M LiHMDS in THF (344 uL, 0.344 mmol) was added to the flask. Upon complete addition the reaction was allowed to warm to room temp. After 2.5 hr 1-benzyl-5-(4-fluorophenyl)-1H-1,2,4-triazol-3-amine (92 mg, 0.344 mmol) in THF (1 mL) was added to the reaction. The reaction was allowed to stir overnight. The next day more 1 M LiHMDS in THF (172 uL, 0.172 mmol) was added. The reaction was stirred an additional 5.5 hr before being quenched with sat. NH4Cl (10 mL). The reaction was diluted with EtOAc (60 mL) and extracted with water (5 mL). The organic phase was dried over Na2SO4 and the solvent evaporated. The residue was purified by silica gel chromatography (60-100 EtOAc/HEP) followed by HPLC (C18, 50-100% MeOH/H2O+5 mM NH4OH) to afford the title compound as a white solid: 1H NMR (400 MHz, DICHLOROMETHANE-d2) 1.58 (d, J=3.92 Hz, 6H) 2.01-2.15 (m, 1H) 2.25-2.36 (m, 1H) 3.36 (t, J=9.22 Hz, 1H) 3.40-3.53 (m, 2H) 3.62-3.70 (m, 1H) 3.87 (t, J=8.21 Hz, 1H) 4.74 (br. s., 1H) 5.44 (s, 2H) 7.19-7.36 (m, 9H) 7.36-7.44 (m, 3H) 7.62-7.70 (m, 2H) 10.76 (br. s., 1H); Rt (method A)=1.61 min (M+H)+=527.2.

後処理

  1. additionUpon complete addition the reaction
  2. stirringThe reaction was stirred an additional 5.5 hr
  3. custombefore being quenched with sat. NH4Cl (10 mL)
  4. additionThe reaction was diluted with EtOAc (60 mL)
  5. extractionextracted with water (5 mL)
  6. dry with materialThe organic phase was dried over Na2SO4
  7. customthe solvent evaporated
  8. customThe residue was purified by silica gel chromatography (60-100 EtOAc/HEP)

出典と根拠

ORDレコード
ord-4e720b8288764c35adaf5704540280e0
出典データセット
uspto-grants-2014_04
特許番号
US08703761B2

反応ノート

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