1,2-Dichloroethane → HCID 178429080, compound

HRID 1050457Notes

Reaction equation

HRID 1050457 reaction equation
[CH2:1]([NH:8][C:9]([C@H:11]1[CH2:16][CH2:15][C@H:14]([O:17][C:18]2[C:19]([CH3:28])=[C:20]([CH:24]=[C:25]([Cl:27])[CH:26]=2)[C:21](O)=[O:22])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[NH2:30][CH2:31][C:32]1[C:37](=[O:38])[CH:36]=[C:35]([CH3:39])[NH:34][C:33]=1[CH3:40].C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1.C([O-])(O)=O.[Na+]>O.CN(C)C=O>[CH2:1]([NH:8][C:9]([C@H:11]1[CH2:12][CH2:13][C@H:14]([O:17][C:18]2[C:19]([CH3:28])=[C:20]([CH:24]=[C:25]([Cl:27])[CH:26]=2)[C:21]([NH:30][CH2:31][C:32]2[C:37](=[O:38])[CH:36]=[C:35]([CH3:39])[NH:34][C:33]=2[CH3:40])=[O:22])[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 516892Sodium BicarbonateHCID 902732273-(aminomethyl)-2,6-dimethylpyridin-4(1H)-one hydrochlorideHCID 178431628HCID 178431628, compound

Product 1

HCID 178429080HCID 178429080, compoundYield 57.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A 20 mL vial was charged with 3-(((trans)-4-(benzylcarbamoyl)cyclohexyl)oxy) -5-chloro-2-methylbenzoic acid (100 mg, 0.249 mmol), 3-(aminomethyl)-2,6-dimethylpyridin-4(1H)-one hydrochloride (56.3 mg, 0.299 mmol), EDC (71.6 mg, 0.373 mmol), HOAt (57.5 mg, 0.373 mmol), N,N-dimethylformamide (3 mL), and N-methylmorpholine (0.274 mL, 2.488 mmol). The reaction was stirred at room temperature for 16 h, at which time it was added to a stirred solution of saturated NaHCO3 (25 mL) and water (10 mL). The precipitate that formed was stirred at room temperature 1 h, then collected via vacuum filtration. The filter cake was dried under high vacuum overnight and diluted with DMSO (1 mL), one drop of 6 N HCl, and 1.25 N HCl in MeOH (2 mL). Most of the sample dissolved after sonication, however additional DMSO (0.5 mL) was added to achieve complete dissolution. The resulting solution was purified by reverse phase HPLC (Column: Phenomenex-NX axia, 30×100, 5μ, C18. Eluent: 25-45% acetonitrile in/0.1% TFA in water) to give 3-(((trans)-4-(benzylcarbamoyl)cyclohexyl)oxy)-5-chloro-N-((2,6-dimethyl-4-oxo-1,4-dihydropyridin -3-yl)methyl)-2-methylbenzamide (77 mg, 0.144 mmol, 57.7% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 13.91 (br. s., 1H), 8.68 (t, J=5.05 Hz, 1H), 8.33 (t, J=5.94 Hz, 1H), 7.28-7.37 (m, 2H), 7.16-7.27 (m, 4H), 6.97 (s, 1H), 6.84 (d, J=2.02 Hz, 1H), 4.38 (d, J=4.80 Hz, 3H), 4.26 (d, J=6.06 Hz, 2H), 2.68 (s, 3H), 2.53-2.55 (m, 3H), 2.23 (tt, J=3.73, 11.56 Hz, 1H), 2.08 (dd, J=3.03, 12.38 Hz, 2H), 2.03 (s, 3H), 1.83 (d, J=11.12 Hz, 2H), 1.50-1.68 (m, 2H), 1.26-1.43 (m, 2H). MS(ES) [M+H]+ 536.3.

Workup

  1. customThe precipitate that formed
  2. stirringwas stirred at room temperature 1 h
  3. filtrationcollected via vacuum filtration
  4. customThe filter cake was dried under high vacuum overnight
  5. additiondiluted with DMSO (1 mL), one drop of 6 N HCl, and 1.25 N HCl in MeOH (2 mL)
  6. dissolutionMost of the sample dissolved
  7. customafter sonication, however additional DMSO (0.5 mL)
  8. additionwas added
  9. dissolutiondissolution
  10. customThe resulting solution was purified by reverse phase HPLC (Column: Phenomenex-NX axia, 30×100, 5μ, C18. Eluent: 25-45% acetonitrile in/0.1% TFA in water)

Sources & evidence

ORD record
ord-41598c36468149ab930de692c537758b
Source dataset
uspto-grants-2016_07
Patent number
US09382234B2

Reaction notes

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