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

HRID 541326노트

반응식

HRID 541326 반응식
[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

참가 물질

8

반응물 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 682888554-(4-Fluoropiperidin-4-yl)benzonitrile hydrochloride2회HCID 178422590HCID 178422590, 화합물2회

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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)+.

후처리

  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)

출처 및 근거

ORD 기록
ord-9793ce43ba9a424290d0eb722a1a5192
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08871790B2

반응 노트

불러오는 중…