Triethylamine → HCID 58721773, compound

HRID 1246815Notes

Reaction equation

HRID 1246815 reaction equation
Cl[C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[C:5]([C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=1[Cl:25])[N:6]2[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=1.[CH:26]([NH:29][C:30]1([C:36]([NH2:38])=[O:37])[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1)([CH3:28])[CH3:27].C(N(CC)CC)C.CO.C(Cl)Cl>C(O)C.C(Cl)Cl>[Cl:17][C:14]1[CH:13]=[CH:12][C:11]([N:6]2[C:5]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=3[Cl:25])=[N:4][C:3]3[C:7]2=[N:8][CH:9]=[N:10][C:2]=3[N:33]2[CH2:32][CH2:31][C:30]([NH:29][CH:26]([CH3:28])[CH3:27])([C:36]([NH2:38])=[O:37])[CH2:35][CH2:34]2)=[CH:16][CH:15]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 967164-(Isopropylamino)piperidine-4-carboxamideHCID 21226129Dichloromethane methanolHCID 219058016-chloro-9-(4-chlorophenyl)-8-(2,4-dichlorophenyl)-9H-purine

Product 1

HCID 58721773HCID 58721773, compound

Reagents, catalysts & solvents 1

HCID 21584144Dichloromethane ethanolSolvent

Conditions

Temperature
60 °C

Procedure

6-Chloro-9-(4-chlorophenyl)-8-(2,4-dichlorophenyl)-9H-purine I-(1A-1)d (300 mg, 0.58 mmol) and 4-isopropylamino-piperidine-4-carboxylic acid amide (101 mg, 0.548 mmol) were suspended in ethanol/methylene chloride (3 ml/1 ml). Triethylamine (0.16 ml, 1.1 mmol) was added to the suspension and the mixture heated to 60° C. until the TLC determined complete (3 h). The reaction mixture was partitioned between saturated NaHCO3 solution and methylene chloride. The organic layer was dried (Na2SO4), filtered, and concentrated to dryness. The pure free base was isolated by silica gel chromatography using 2–4% methanol/methylene chloride as the gradient eluant to afford title compound 10A-1. A solution of the material in methylene chloride was treated with excess 1 N HCl in diethyl ether, stirred, evaporated to dryness, and then triturated in diethyl ether to afford the hydrochloride salt of compound 10A-1 as a tan solid (115 mg, 38%): +ESI MS (M+1) 558.2; 1H NMR (400 MHz, CD3OD) δ 8.40 (s, 1H), 7.60 (d, J=8.3 Hz, 1H), 7.56 (d, J=2.1 Hz, 1H), 7.51–7.44 (m, 3H), 7.33 (d, J=8.7 Hz, 2H), 5.20 (v br m, 2H), 3.87 (br m, 2H), 3.59 (septuplet, J=6.6 Hz, 1H), 2.68 (br d, J=13.7 Hz, 2H), 2.16 (ddd, J=14.5, 10.4, 4.1 Hz, 2H), 1.39 (d, J=6.6 Hz, 6H).

Workup

  1. custom(3 h)
  2. customThe reaction mixture was partitioned between saturated NaHCO3 solution and methylene chloride
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customThe pure free base was isolated by silica gel chromatography

Sources & evidence

ORD record
ord-f66f6433427d41f280d65e767e83d6c0
Source dataset
uspto-grants-2006_10
Patent number
US07129239B2

Reaction notes

Loading…