2,3-Dichlorobenzoic acid → 2,3-Dichloro-N-[[4,4-difluoro-1-(6-fluoro-3-pyridyl)cyclohexyl]methyl]benzamide

HRID 512226노트

반응식

HRID 512226 반응식
[F:1][C:2]1([F:17])[CH2:7][CH2:6][C:5]([CH2:15][NH2:16])([C:8]2[CH:9]=[N:10][C:11]([F:14])=[CH:12][CH:13]=2)[CH2:4][CH2:3]1.[Cl:18][C:19]1[C:27]([Cl:28])=[CH:26][CH:25]=[CH:24][C:20]=1[C:21](O)=[O:22].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.CCN(C(C)C)C(C)C>CN(C=O)C.O>[Cl:18][C:19]1[C:27]([Cl:28])=[CH:26][CH:25]=[CH:24][C:20]=1[C:21]([NH:16][CH2:15][C:5]1([C:8]2[CH:9]=[N:10][C:11]([F:14])=[CH:12][CH:13]=2)[CH2:4][CH2:3][C:2]([F:1])([F:17])[CH2:7][CH2:6]1)=[O:22]

참가 물질

8

반응물 5

HCID 57652,3-Dichlorobenzoic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86716261[4,4-Difluoro-1-(6-fluoro-pyridin-3-yl)-cyclohexyl]-methylamine

생성물 1

HCID 867162602,3-Dichloro-N-[[4,4-difluoro-1-(6-fluoro-3-pyridyl)cyclohexyl]methyl]benzamide수율 38.2%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

A solution of C-[4,4-difluoro-1-(6-fluoro-pyridin-3-yl)-cyclohexyl]-methylamine (38 mg, 0.157 mmol), 2,3-dichlorobenzoic acid (30 mg, 0.157 mmol), HOBt (25 mg, 0.185 mmol), EDCI.HCl (36 mg, 0.185 mmol) and DIPEA (48 mg, 0.345 mmol) in DMF (2 mL) was stirred at room temperature overnight. Water was added to the solution followed by extraction with EtOAc (3×10 ml). The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude product was purified by Prep. HPLC to give the title compound (25 mg, yield: 38%). 1H NMR (CDCl3 300 MHz): δ ppm 8.18 (d, J=2.8 Hz, 1H), 7.89-7.80 (m, 1H), 7.50 (dd, J=8.0 Hz, 2.0 Hz, 1H), 7.33 (dd, J=7.6 Hz, 1.6 Hz, 1H), 7.28-7.18 (m, 1H), 6.98 (dd, J=8.8 Hz, 3.2 Hz, 1H), 5.85 (t, J=6.8 Hz, 1H), 3.64 (d, J=6.8 Hz, 2H), 2.36-2.00 (m, 6H), 1.87-1.65 (m, 2H). LCMS (MH+): m/z=417.1, tR (minutes, Method C)=1.11

후처리

  1. extractionfollowed by extraction with EtOAc (3×10 ml)
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product was purified by Prep

출처 및 근거

ORD 기록
ord-0f306096c9854ebaaa1c391b1fdd9c55
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09102591B2

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