Ethyl orthoformate → 2-[(S)-1-Phenylethylamino]-4-[5-(tetrazol-1-yl)-benzimidazol-1-yl]pyrimidine

HRID 2300809Notes

Reaction equation

HRID 2300809 reaction equation
[C:1]1([C@@H:7]([NH:9][C:10]2[N:15]=[C:14]([N:16]3[C:20]4[CH:21]=[CH:22][C:23]([NH2:25])=[CH:24][C:19]=4[N:18]=[CH:17]3)[CH:13]=[CH:12][N:11]=2)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:26](OCC)(OCC)OCC.[N-:36]=[N+:37]=[N-:38].[Na+]>C(O)(=O)C>[C:1]1([C@@H:7]([NH:9][C:10]2[N:15]=[C:14]([N:16]3[C:20]4[CH:21]=[CH:22][C:23]([N:25]5[CH:26]=[N:38][N:37]=[N:36]5)=[CH:24][C:19]=4[N:18]=[CH:17]3)[CH:13]=[CH:12][N:11]=2)[CH3:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 31214Ethyl orthoformateHCID 33557Sodium AzideHCID 98839772-[(S)-1-phenylethylamino]-4-[5-aminobenzimidazol-1-yl]pyrimidine

Product 1

HCID 99299172-[(S)-1-Phenylethylamino]-4-[5-(tetrazol-1-yl)-benzimidazol-1-yl]pyrimidine

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of 2-[(S)-1-phenylethylamino]-4-[5-aminobenzimidazol-1-yl]pyrimidine (EXAMPLE 79) (80 mg) in acetic acid (2 mL) was added triethyl orthoformate (123 μL). The reaction was stirred at room temperature for 1 h, at 75° C. for 2 h, and then at room temperature again overnight (≈14 h). NaN3 (47 mg, 3 eq.) was added; the reaction was stirred at 75° C. for 5 h. The reaction was cooled, quenched with water, extracted with methylene chloride. The organic solution was washed with water and brine; it was dried over Na2SO4. Removal of the solvent and subsequent purification by preparative thin layer chromatography (acetone:hexane=1:1) provided the title compound (20 mg). Mass spectrum (ESI): 384 (M+1). 1H NMR (500 MHz, CDCl3): δ 9.04 (s, 1H); 8.56 (br s, 1H); 8.46 (d, J=5.2 Hz, 1H); 8.08 (s, 1H); 7.82 (br s, 1H); 7.57 (br s, 1H); 7.50-7.25 (m, 5H); 6.79 (d, J=5.3 Hz, 1H); 5.88 (br s, 1H); 5.18 (br s, 1H); 1.67 (d, J=6.8 Hz, 3H).

Workup

  1. customat room temperature
  2. customagain overnight (≈14 h)
  3. stirringthe reaction was stirred at 75° C. for 5 h
  4. temperatureThe reaction was cooled
  5. customquenched with water
  6. extractionextracted with methylene chloride
  7. washThe organic solution was washed with water and brine
  8. dry with materialit was dried over Na2SO4
  9. customRemoval of the solvent and subsequent purification by preparative thin layer chromatography (acetone:hexane=1:1)

Sources & evidence

ORD record
ord-1937430679414d2ca0e0093d3f0bc29b
Source dataset
uspto-grants-2002_12
Patent number
US06498165B1

Reaction notes

Loading…