Water → 4-[4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-phenylamine

HRID 1773867Notes

Reaction equation

HRID 1773867 reaction equation
C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[N:23]=[C:22]3[N:16]([CH2:17][CH2:18][C:19]4[CH:35]=[CH:34][CH:33]=[CH:32][C:20]=4[CH:21]3[O:24][CH:25]3[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]3)[CH:15]=2)=[CH:10][CH:9]=1)(C)(C)C.FC(F)(F)C(O)=O.O.[OH-].[Na+]>C(Cl)Cl>[CH3:31][N:28]1[CH2:27][CH2:26][CH:25]([O:24][CH:21]2[C:20]3[CH:32]=[CH:33][CH:34]=[CH:35][C:19]=3[CH2:18][CH2:17][N:16]3[C:22]2=[N:23][C:14]([C:11]2[CH:10]=[CH:9][C:8]([NH2:7])=[CH:13][CH:12]=2)=[CH:15]3)[CH2:30][CH2:29]1

Participants

6

Reactant 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 72694266HCID 72694266, compound

Product 1

HCID 867039544-[4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-phenylamine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of {4-[4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-phenyl}-carbamic acid tert-butyl ester (example 49A) (45 mg, 0.092 mmole) in CH2Cl2 (0.3 mL) is added trifluoroacetic acid (90 μL). The reaction mixture is stirred at room temperature for 1 hour. Water is added and pH adjusted to 9-10 with 1N NaOH. The aqueous phase is extracted three times with CH2Cl2. The organic phase is dried over magnesium sulphate, filtered and the solvent is removed under reduced pressure. The residue is purified by silica gel chromatography using (CH2Cl2:MeOH:NH4OH) as eluent with a gradient from (98:2:0.2) to (95:5:0.5) to give 4-[4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-phenylamine melting at 197° C.

Workup

  1. extractionThe aqueous phase is extracted three times with CH2Cl2
  2. dry with materialThe organic phase is dried over magnesium sulphate
  3. filtrationfiltered
  4. customthe solvent is removed under reduced pressure
  5. customThe residue is purified by silica gel chromatography

Sources & evidence

ORD record
ord-f57c4e5fd2ec4d8493339129c9eaeacc
Source dataset
uspto-grants-2016_02
Patent number
US09255101B2

Reaction notes

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