Acetic Anhydride → HCID 178441727, compound

HRID 719556Notes

Reaction equation

HRID 719556 reaction equation
[CH2:1]([C:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:23]3[NH:27][N:26]=[N:25][N:24]=3)=[CH:13][CH:12]=2)[N:8]=[C:7]([CH2:28][NH2:29])[N:6]=1)[CH2:2][CH2:3][CH3:4].C(=O)([O-])[O-].[K+].[K+].[C:36](OC(=O)C)(=[O:38])[CH3:37]>O>[CH2:1]([C:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:23]3[NH:27][N:26]=[N:25][N:24]=3)=[CH:13][CH:12]=2)[N:8]=[C:7]([CH2:28][NH:29][C:36](=[O:38])[CH3:37])[N:6]=1)[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 11430Potassium Carbonate3×HCID 178441733HCID 178441733, compound

Product 1

HCID 178441727HCID 178441727, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

A 92.9 mg (0.22 mmol) sample of 5-[4′-[(5-butyl-3-methylamine-1H-1,2,4-triazol-1-yl)methyl]-(1,1′-biphenyl-2-yl]-1H-tetrazole hydrochloride from Example 27 was dissolved in 5 ml of water and the pH was adjusted to 9 with 1M potassium carbonate (K2CO3). The solution was cooled to 0° C. and 0.22 ml of 1M K2CO3 was added followed by 0.22 mmol of acetic anhydride. Additional K2CO3 was added as needed to maintain a pH of 9. At 30 min intervals, this addition was repeated until analytical reverse phase chromatography showed that all starting material has been consumed. The pH was adjusted to three with 1N HCl and extracted with ethyl acetate. The ethyl acetate was removed in vacuo and the product lyophilized from acetonitrile/water providing 36 mg (39%) of N-[[5-butyl-1-[2′-(1H-tetrazol-5-yl) [1,1′-biphenyl]-4-ylmethyl]-1H-1,2,4-triazol-3-yl]methyl]acetamide as a colorless solid: NMR (CDCl3) δ0.80 (t, J=8 Hz, 3H), 1.18–1.37 (m, 2H), 1.47–1.64 (m, 2H), 1.94 (s, 3H), 2.63 (t, J=8 Hz, 2H), 4.22 (d, J=8 Hz, 2H), 5.18 (s, 2H), 6.95 (d, J=8 Hz, 2H), 7.04–7.21 (m, 2H), 7.44 (d, J=8 Hz, 1H), 7.50–7.66 (m, 2H), 7.90 (dd, J=8 and 2 Hz, 1H); MS (FAB) m/e (rel intensity) 431 (42), 207 (100); HRMS. Calc'd for M+H: 431.2308. Found: 431.2271.

Workup

  1. temperatureto maintain a pH of 9
  2. additionthis addition
  3. customhas been consumed
  4. extractionextracted with ethyl acetate
  5. customThe ethyl acetate was removed in vacuo

Sources & evidence

ORD record
ord-ebd83127eff84ab0ba04929d618952f1
Source dataset
uspto-grants-2006_11
Patent number
US07132437B2

Reaction notes

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