Triethylamine → (4-{3-[4-(3,3-dimethyl-butyl)-piperazin-1-yl]-propoxy}-3-fluorophenyl)-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulen-9-yl)-methanone

HRID 220874Notes

Reaction equation

HRID 220874 reaction equation
[CH3:1][C:2]([CH3:7])([CH3:6])[CH2:3][CH:4]=O.C(N(CC)CC)C.Cl.Cl.[F:17][C:18]1[CH:19]=[C:20]([C:34]([N:36]2[CH2:45][C:44]3[CH:43]=[N:42][N:41]([CH3:46])[C:40]=3[NH:39][C:38]3[CH:47]=[CH:48][CH:49]=[CH:50][C:37]2=3)=[O:35])[CH:21]=[CH:22][C:23]=1[O:24][CH2:25][CH2:26][CH2:27][N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1.C([BH3-])#N.[Na+]>CO.C(O)(=O)C>[CH3:1][C:2]([CH3:7])([CH3:6])[CH2:3][CH2:4][N:31]1[CH2:32][CH2:33][N:28]([CH2:27][CH2:26][CH2:25][O:24][C:23]2[CH:22]=[CH:21][C:20]([C:34]([N:36]3[CH2:45][C:44]4[CH:43]=[N:42][N:41]([CH3:46])[C:40]=4[NH:39][C:38]4[CH:47]=[CH:48][CH:49]=[CH:50][C:37]3=4)=[O:35])=[CH:19][C:18]=2[F:17])[CH2:29][CH2:30]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 763353,3-DimethylbutanalHCID 5003444Sodium cyanoborohydrideHCID 135736023[3-Fluoro-4-(3-piperazin-1-yl-propoxy)-phenyl]-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulen-9-yl)-methanone Dihydrochloride

Product 1

HCID 135414518(4-{3-[4-(3,3-dimethyl-butyl)-piperazin-1-yl]-propoxy}-3-fluorophenyl)-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulen-9-yl)-methanone

Reagents, catalysts & solvents 1

HCID 10129899Acetic acid methanolSolvent

Procedure

3,3-Dimethylbutyraldehyde (120 mg, 1.20 mmol) and triethylamine (to pH9) were added to a solution of [3-fluoro-4-(3-piperazin-1-yl-propoxy)-phenyl]-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulen-9-yl)-methanone dihydrochloride from Example E49 (585 mg, 1.09 mmol) in methanol/acetic acid (99:1, v/v, 20 ml) and the mixture was stirred at room temperature for 1 h. Sodium cyanoborohydride (103 mg, 1.30 mmol) was added and the mixture was stirred at room temperature for 18 h then concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; 10% methanol:90% dichloromethane) to yield (4-{3-[4-(3,3-dimethyl-butyl)-piperazin-1-yl]-propoxy}-3-fluoro-phenyl)-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulen-9-yl)-methanone, which was lyophilised from aqueous trifluoroacetic acid to give a white solid identified as the title compound (700 mg, 83%).

Workup

  1. stirringthe mixture was stirred at room temperature for 18 h
  2. concentrationthen concentrated in vacuo
  3. customThe residue was purified by flash chromatography on silica gel (eluant; 10% methanol:90% dichloromethane)

Sources & evidence

ORD record
ord-ac0d305fbee4447e8df157e7d2d0084f
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

Loading…