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

HRID 512226Notes

Reaction equation

HRID 512226 reaction equation
[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]

Participants

8

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

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

Workup

  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

Sources & evidence

ORD record
ord-0f306096c9854ebaaa1c391b1fdd9c55
Source dataset
uspto-grants-2015_08
Patent number
US09102591B2

Reaction notes

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