Diisopropylethylamine → 4-(1-(4-Cyclobutyl-2-methyl-5-(4H-1,2,4-triazol-3-yl)benzoyl)-4-fluoropiperidin-4-yl)benzonitrile

HRID 541326ノート

反応式

HRID 541326 の反応式
[CH:1]1([C:5]2[C:13]([C:14]3[NH:18][CH:17]=[N:16][N:15]=3)=[CH:12][C:8]([C:9]([OH:11])=O)=[C:7]([CH3:19])[CH:6]=2)[CH2:4][CH2:3][CH2:2]1.Cl.[F:21][C:22]1([C:28]2[CH:35]=[CH:34][C:31]([C:32]#[N:33])=[CH:30][CH:29]=2)[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1.O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.CCN(C(C)C)C(C)C>C(OCC)(=O)C.CN(C=O)C>[CH:1]1([C:5]2[C:13]([C:14]3[NH:18][CH:17]=[N:16][N:15]=3)=[CH:12][C:8]([C:9]([N:25]3[CH2:26][CH2:27][C:22]([C:28]4[CH:35]=[CH:34][C:31]([C:32]#[N:33])=[CH:30][CH:29]=4)([F:21])[CH2:23][CH2:24]3)=[O:11])=[C:7]([CH3:19])[CH:6]=2)[CH2:2][CH2:3][CH2:4]1

参加物

8

反応物 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 682888554-(4-Fluoropiperidin-4-yl)benzonitrile hydrochloride2 回HCID 178422590HCID 178422590、化合物2 回

生成物 1

HCID 1784225894-(1-(4-Cyclobutyl-2-methyl-5-(4H-1,2,4-triazol-3-yl)benzoyl)-4-fluoropiperidin-4-yl)benzonitrile収率 56.4%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a 4-mL vial was added 4-cyclobutyl-2-methyl-5-(4H-1,2,4-triazol-3-yl)benzoic acid (compound 202.3, 31 mg, 0.12 mmol, 1.0 equiv), 4-(4-fluoropiperidin-4-yl)benzonitrile (compound 11.2, 31 mg, 0.13 mmol, 1.1 equiv), 1-hydroxybenzotriazole hydrate (20 wt % water) (25 mg, 0.15 mmol, 1.25 equiv), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (25 mg, 0.13 mmol, 1.1 equiv), DMF (0.6 mL) and DIEA (83 μL, 0.48 mmol, 4 equiv). The mixture was stiffed at room temperature for 4 hours then diluted with ethyl acetate (10 mL) and washed with 1 M NaH2PO4 (5 mL). The aqueous was back extracted with ethyl acetate (3 mL) and the combined organics was washed with brine (5 mL), saturated NaHCO3 (5 mL) and brine (5 mL). The organics were dried (Na2SO4), filtered and removed in vacuo. The crude residue was purified by preparative TLC (DCM/8% MeOH) to obtain the title compound as a white solid (30 mg, 56%). m/z (ES+) 444 (M+H)+.

後処理

  1. washwashed with 1 M NaH2PO4 (5 mL)
  2. extractionThe aqueous was back extracted with ethyl acetate (3 mL)
  3. washthe combined organics was washed with brine (5 mL), saturated NaHCO3 (5 mL) and brine (5 mL)
  4. dry with materialThe organics were dried (Na2SO4)
  5. filtrationfiltered
  6. customremoved in vacuo
  7. customThe crude residue was purified by preparative TLC (DCM/8% MeOH)

出典と根拠

ORDレコード
ord-9793ce43ba9a424290d0eb722a1a5192
出典データセット
uspto-grants-2014_10
特許番号
US08871790B2

反応ノート

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