4-Methylmorpholine → 3-Ethoxy-2-hydroxy-5-(2-oxo-5,6-diphenyl-1,2,3,4-tetrahydropyrimidin-4-yl)benzamide

HRID 2177938Notes

Reaction equation

HRID 2177938 reaction equation
[CH2:1]([O:3][C:4]1[C:5]([OH:32])=[C:6]([CH:10]=[C:11]([CH:13]2[C:18]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[C:17]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[NH:16][C:15](=[O:31])[NH:14]2)[CH:12]=1)[C:7]([OH:9])=O)[CH3:2].[NH4+].[Cl-].CC[N:37]=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>CN(C=O)C>[CH2:1]([O:3][C:4]1[C:5]([OH:32])=[C:6]([CH:10]=[C:11]([CH:13]2[C:18]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[C:17]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[NH:16][C:15](=[O:31])[NH:14]2)[CH:12]=1)[C:7]([NH2:37])=[O:9])[CH3:2]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 513486643-Ethoxy-2-hydroxy-5-(2-oxo-5,6-diphenyl-1,2,3,4-tetrahydropyrimidin-4-yl)benzoic acid

Product 1

HCID 513486663-Ethoxy-2-hydroxy-5-(2-oxo-5,6-diphenyl-1,2,3,4-tetrahydropyrimidin-4-yl)benzamideYield 16.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of Compound 77 (described previously) (280 mg, 0.65 mmol), NH4Cl (41 mg, 0.78 mmol), EDCI (149 mg, 0.78 mmol), HOBT (105 mg, 0.78 mmol), and NMM (0.29 mL, 2.6 mmol) in DMF (5 mL) was stirred at room temperature for two hours. LCMS showed most of the starting material was consumed. 100 mL of a mixture of EtOAc and MeOH (v/v=10:1) was added to dilute the mixture. The organic layer was washed with brine (20 mL×2), dried over Na2SO4, filtered, concentrated, and purified by preparative HPLC to afford Compound 82 as a yellow solid (46 mg, yield: 16.4%). 1H NMR (DMSO-d6 400 MHz): δ 12.94 (s, 1H), 8.58 (s, 1H), 8.30 (s, 1H), 7.86 (s, 1H), 7.37 (s, 1H), 7.33 (s, 1H), 7.20-7.25 (m, 5H), 7.11 (s, 1H), 6.97-7.02 (m, 3H), 6.80 (d, J=6.8 Hz, 2H), 5.10 (d, J=2.4 Hz, 1H), 4.00 (q, J=7.2 Hz, 2H), 1.32 (t, J=6.8 Hz, 3H); MS (ESI): m/z 430.1 [M+1]+.

Workup

  1. customwas consumed
  2. addition100 mL of a mixture of EtOAc and MeOH (v/v=10:1) was added
  3. additionto dilute the mixture
  4. washThe organic layer was washed with brine (20 mL×2)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-a10089c25c144d578936cca48fce67b0
Source dataset
uspto-grants-2015_06
Patent number
US09067893B2

Reaction notes

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