1,1'-Carbonyldiimidazole → HCID 58996983, compound

HRID 251000Notes

Reaction equation

HRID 251000 reaction equation
[CH3:1][C:2]1[C:3]([CH2:9][N:10]([CH2:16][C:17]2[C:22]([C:23]([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=3)([CH3:25])[CH3:24])=[CH:21][CH:20]=[CH:19][N:18]=2)[CH2:11][CH2:12][CH2:13][CH2:14][NH2:15])=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1.[C:33]([N:40]1C=CN=C1)(N1C=CN=C1)=[O:34].CCN(C(C)C)C(C)C.N[OH:55].Cl>C1COCC1.C(Cl)Cl>[CH3:1][C:2]1[C:3]([CH2:9][N:10]([CH2:16][C:17]2[C:22]([C:23]([CH3:25])([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=3)[CH3:24])=[CH:21][CH:20]=[CH:19][N:18]=2)[CH2:11][CH2:12][CH2:13][CH2:14][NH:15][C:33]([NH:40][OH:55])=[O:34])=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 443297Hydroxyamine hydrochlorideHCID 11293450HCID 11293450, compound

Product 1

HCID 58996983HCID 58996983, compoundYield 60.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of N1-(3,5-Dimethyl-pyridin-2-ylmethyl)-N1-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-pyridin-2-ylmethyl}-butane-1,4-diamine (0.210 g, 0.48 mmol) in dry THF (4 mL) was added 1,1′-carbonyldiimidazole (79 mg, 0.49 mmol), and the resultant solution was stirred room temperature for 30 minutes. The mixture was concentrated and the resultant oil was dissolved in DMF (2 mL), treated with DIPEA (0.50 mL, 2.87 mmol) and NH2OH.HCl (134 mg, 1.93 mmol), and heated at 60° C. overnight. The mixture was cooled to room temperature, diluted with CH2Cl2 (50 mL), washed with brine (3×10 mL), dried (Na2SO4) and concentrated. Purification of the crude material by column chromatography on silica gel (20:21:1 CH2Cl2-MeOH—NH4OH) provided 143 mg (59%) of COMPOUND 149 as a white solid. 1H NMR (CDCl3) δ 1.34 (br s, 4H), 1.65 (s, 6H), 1.93-2.25 (m, 8H), 3.09 (d, 2H, J=5.1 Hz), 3.32 (s, 2H), 3.45 (s, 2H), 6.87-7.09 (m, 5H), 7.21-7.38 (m, 3H), 7.89 (d, 1H, J=7.2 Hz), 8.14 (s, 1H), 8.53 (d, 1H, J=3.3 Hz), 10.27 (br s, 1H); 13C NMR (CDCl3) δ 18.26, 18.75, 23.87, 28.13, 31.51, 39.41, 42.50, 53.98, 57.19, 58.03, 115.56 (d, JC-F=21 Hz), 122.18, 127.72 (d, JC-F=7.5 Hz), 132.12, 132.87, 134.56, 139.50, 143.67, 145.71, 146.71, 146.97, 153.38, 157.78, 161.31 (d, JC-F=243 Hz), 162.84; ES-MS m/z 494 (M+H). Anal. Calcd. For C28H36N5O2F.0.7H2O: C, 66.43; H, 7.45; N, 13.83; F, 3.75. Found: C, 66.04; H, 7.29; N, 14.22; F, 3.85.

Workup

  1. concentrationThe mixture was concentrated
  2. dissolutionthe resultant oil was dissolved in DMF (2 mL)
  3. temperatureThe mixture was cooled to room temperature
  4. washwashed with brine (3×10 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customPurification of the crude material by column chromatography on silica gel (20:21:1 CH2Cl2-MeOH—NH4OH)

Sources & evidence

ORD record
ord-11ca7cd6fbec4b5b9d89a6fafa59d2b9
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

Loading…