Water → HCID 178441694, compound

HRID 1361905Notes

Reaction equation

HRID 1361905 reaction equation
[C:1](=[O:21])([O:17][CH:18](Cl)[CH3:19])[O:2][CH2:3][CH2:4][CH2:5][CH2:6][C@@H:7]([O:13][N+:14]([O-:16])=[O:15])[CH2:8][O:9][N+:10]([O-:12])=[O:11].[CH2:22]([C:26]1[N:27]([CH2:35][C:36]2[CH:41]=[CH:40][C:39]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=3[C:48]3[N:52](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:51]=[N:50][N:49]=3)=[CH:38][CH:37]=2)[C:28]([C:32]([OH:34])=[O:33])=[C:29]([Cl:31])[N:30]=1)[CH2:23][CH2:24][CH3:25].C([O-])([O-])=O.[Cs+].[Cs+].O>CN(C=O)C>[CH2:22]([C:26]1[N:27]([CH2:35][C:36]2[CH:41]=[CH:40][C:39]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=3[C:48]3[NH:52][N:51]=[N:50][N:49]=3)=[CH:38][CH:37]=2)[C:28]([C:32]([O:34][CH:18]([O:17][C:1]([O:2][CH2:3][CH2:4][CH2:5][CH2:6][C@@H:7]([O:13][N+:14]([O-:16])=[O:15])[CH2:8][O:9][N+:10]([O-:12])=[O:11])=[O:21])[CH3:19])=[O:33])=[C:29]([Cl:31])[N:30]=1)[CH2:23][CH2:24][CH3:25]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 467832052-Butyl-4-chloro-1-({2'-[1-(triphenylmethyl)-1H-tetrazol-5-yl][1,1'-biphenyl]-4-yl}methyl)-1H-imidazole-5-carboxylic acidHCID 59370672(5R)-5,6-bis(nitrooxy)hexyl 1-chloroethyl carbonate

Product 1

HCID 178441694HCID 178441694, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

(5R)-5,6-bis(nitrooxy)hexyl 1-chloroethyl carbonate (7.67 g, 23.2 mmol) was added to a stirred solution of 2-butyl-4-chloro-1-{[2′-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazole-5-carboxylic acid (6.30 g, 9.3 mmol) and Cs2CO3 (3.02 g, 9.3 mmol) in DMF (186 mL). The solution was stirred at 70° C. for 2 h. Water (50 mL) was added and the solution was extracted with EtOAc (3×100 mL). The combined organic layers were dried (MgSO4), filtered, and concentrated in vacuo. The residue was redissolved in MeOH (186 mL). After stirring at 70° C. for 2 h, the solution was concentrated in vacuo. The residue was purified by HPLC chromatography (50×100 mm C-18) eluting with 40-100% MeCN/water+0.05% TFA. The diastereomers were then separated by HPLC chromatography on silica gel (ChiralPak AD-H) eluting with 20% MeOH in supercritical CO2 to give the title compound as a white solid. 1H NMR (500 MHz, CD3OD) δ 8.06 (d, J=7.5 Hz, 1H), 7.62 (td, J=7.5, 1.0 Hz, 1H), 7.56 (td, J=6.5, 1.0 Hz, 1H), 7.44 (d, J=6.5 Hz, 1H), 7.17 (d, J=8.0 Hz, 2H), 6.99 (d, J=8.0 Hz, 2H), 6.87 (q, J=5.5 Hz, 1H), 5.54 (d, J=6.0 Hz, 2H), 5.24 (ddd, J=13.0, 6.2, 3.0 Hz, 1H), 4.73 (dq, J=12.5, 1.5 Hz, 1H), 4.46 (dd, J=13.0, 6.5 Hz, 1H), 4.14-4.04 (m, 1H), 2.76 (t, J=7.7 Hz, 2H), 1.76-1.59 (m, 6H), 1.61 (d, J=5.5 Hz, 3H) 1.55-1.40 (m, 2H), 1.38 (hex, J=7.5 Hz, 2H), 0.90 (t, J=7.5 Hz, 3H); LCMS (M+H) found 731.1.

Workup

  1. extractionthe solution was extracted with EtOAc (3×100 mL)
  2. dry with materialThe combined organic layers were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was redissolved in MeOH (186 mL)
  6. stirringAfter stirring at 70° C. for 2 h
  7. concentrationthe solution was concentrated in vacuo
  8. customThe residue was purified by HPLC chromatography (50×100 mm C-18)
  9. washeluting with 40-100% MeCN/water+0.05% TFA
  10. customThe diastereomers were then separated by HPLC chromatography on silica gel (ChiralPak AD-H)
  11. washeluting with 20% MeOH in supercritical CO2

Sources & evidence

ORD record
ord-f83ed84067114f5f87f6f5701aa99126
Source dataset
uspto-grants-2011_02
Patent number
US07880014B2

Reaction notes

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