Acetic Acid → HCID 11153699, compound

HRID 1809158Notes

Reaction equation

HRID 1809158 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][CH:23]=1)[CH2:5][NH:6][C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([C:17]([F:20])([F:19])[F:18])[CH:11]=1)=[O:8].C(OCC)(OCC)OCC.[N-:34]=[N+:35]=[N-:36].[Na+].[C:38](O)(=O)C.Cl.N([O-])=O.[Na+]>O>[Cl:16][C:13]1[CH:14]=[CH:15][C:10]([NH:9][C:7]([NH:6][CH2:5][C:4]2[CH:21]=[CH:22][CH:23]=[C:2]([N:1]3[CH:38]=[N:36][N:35]=[N:34]3)[CH:3]=2)=[O:8])=[CH:11][C:12]=1[C:17]([F:20])([F:18])[F:19]

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 31214Ethyl orthoformateHCID 33557Sodium AzideHCID 23668193Sodium NitriteHCID 59708718HCID 59708718, compound

Product 1

HCID 11153699HCID 11153699, compoundYield 6.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a round bottom flask was added urea 27 (100 mg, 0.29 mmol, 1.0 eq.), triethyl orthoformate (0.16 mL, 0.93 mmol, 6.4 eq.), sodium azide (25.0 mg, 0.36 mmol, 1.25 eq.), and acetic acid (0.26 ml, 4.64 mmol, 16.0 eq.). The reaction mixture was stirred at RT for 10 min. before heating to 75° C. for 1 h. The reaction was cooled to RT, and water (0.2 mL), 6N HCl (0.16 mL), and 25% aq. NaNO2 (0.064 mL). The mixture was then extracted with EtOAc, washed with brine and dried with Na2SO4. Concentration via rotary evaporation followed by silica gel column chromatography with 60:40 EtOAc: Hexanes afforded urea 28 as a yellow solid (7.5 mg, 6% yield). LC/MSD (HP Series 1100 MSD) MS (ES+) m/z 397.0 (M+H)+1 1H-NMR, Varian 400 MHz (DMSO-d6) δ 10.40 (s, 1H), 9.24 (s, 1H), 8.30 (d, 1H), 7.82 (s, 1H), 7.79 (d, 1H), 7.62-7.42 (m, 4H), 7.10 (t, 1H), 4.40 (s, 2H) ppm.

Workup

  1. temperaturebefore heating to 75° C. for 1 h
  2. temperatureThe reaction was cooled to RT
  3. extractionThe mixture was then extracted with EtOAc
  4. washwashed with brine
  5. dry with materialdried with Na2SO4
  6. concentrationConcentration
  7. customvia rotary evaporation

Sources & evidence

ORD record
ord-6953b113da8d487d999e14ebaac31de8
Source dataset
uspto-grants-2013_01
Patent number
US08362017B2

Reaction notes

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