Sodium Hydroxide → HCID 86703987, compound

HRID 1773909Notes

Reaction equation

HRID 1773909 reaction equation
[CH3:1][C:2]1[N:11]2[C:5]([CH:6]([O:16][CH:17]3[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]3)[C:7]3[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=3[CH2:9][CH2:10]2)=[N:4][C:3]=1[C:24]1[CH:29]=[CH:28][C:27]([NH2:30])=[CH:26][CH:25]=1.CCN(C(C)C)C(C)C.[C:40]([N:44]=[C:45]=[O:46])([CH3:43])([CH3:42])[CH3:41].[OH-].[Na+]>C(#N)C.O>[C:40]([NH:44][C:45]([NH:30][C:27]1[CH:28]=[CH:29][C:24]([C:3]2[N:4]=[C:5]3[N:11]([CH2:10][CH2:9][C:8]4[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=4[CH:6]3[O:16][CH:17]3[CH2:18][CH2:19][N:20]([CH3:23])[CH2:21][CH2:22]3)[C:2]=2[CH3:1])=[CH:25][CH:26]=1)=[O:46])([CH3:43])([CH3:42])[CH3:41]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 62412tert-Butyl isocyanateHCID 81531DiisopropylethylamineHCID 86703979HCID 86703979, compound

Product 1

HCID 86703987HCID 86703987, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 4-[1-methyl-4-(1-methyl piperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-phenylamine (example 173) (50 mg, 0.124 mmole) in ACN (1 mL) are added DIEA (65 μL, 0.372 mmole) and tertbutylisocyanate (21 μL, 0.182 mmole). The reaction mixture is heated overnight at 80° C. Water is added as well as 1N NaOH to pH 10. The aqueous phase is extracted three times with CH2Cl2. The organic phase is dried over MgSO4, filtered, and the solvent is removed under reduced pressure. The residue is pre-purified by silica gel chromatography eluting with (CH2Cl2:MeOH:NH4OH) from (98:2:0.2) to (95:5:0.5), and the residue is submitted to a preparative TLC on silica gel eluting with (CH2Cl2:MeOH:NH4OH) from (9:1:1) to give 1-tert-butyl-3-{4-[1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-phenyl}-urea melting at 173° C.

Workup

  1. extractionThe aqueous phase is extracted three times with CH2Cl2
  2. dry with materialThe organic phase is dried over MgSO4
  3. filtrationfiltered
  4. customthe solvent is removed under reduced pressure
  5. customThe residue is pre-purified by silica gel chromatography
  6. washeluting with (CH2Cl2:MeOH:NH4OH) from (98:2:0.2) to (95:5:0.5)

Sources & evidence

ORD record
ord-b4cee5ac025949668d2d074b5a320cf0
Source dataset
uspto-grants-2016_02
Patent number
US09255101B2

Reaction notes

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