Trifluoroacetic acid → HCID 57756221, compound

HRID 911146Notes

Reaction equation

HRID 911146 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]3[C:21]([C:22]4[CH:27]=[CH:26][N:25]=[C:24]([NH:28][CH3:29])[N:23]=4)=[CH:20][CH:19]=[CH:18][N:17]=3)=[CH:11][CH:10]=2)=[C:4]2[CH2:30][CH2:31][CH2:32][C:3]=12.[NH:33]1[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1.C(O)(C(F)(F)F)=O>CC(O)CC.[OH-].[Na+].O.CCOC(C)=O>[CH3:29][NH:28][C:24]1[N:23]=[C:22]([C:21]2[C:16]([O:15][C:12]3[CH:13]=[CH:14][C:9]([NH:8][C:5]4[N:6]=[N:7][C:2]([N:33]5[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]5)=[C:3]5[CH2:32][CH2:31][CH2:30][C:4]=45)=[CH:10][CH:11]=3)=[N:17][CH:18]=[CH:19][CH:20]=2)[CH:27]=[CH:26][N:25]=1

Participants

8

Reactant 3

HCID 6422Trifluoroacetic acidHCID 8082PiperidineHCID 86614165HCID 86614165, compound

Product 1

HCID 57756221HCID 57756221, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6568(+-)-2-ButanolSolventHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
125 °C

Procedure

To a mixture of 4-chloro-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-6,7-dihydro-5H-cyclopenta[d]pyridazin-1-amine (0.200 g, 0.449 mmol) and piperidine (0.310 ml, 3.14 mmol) in 2 mL 2-butanol was added TFA (0.173 ml, 2.24 mmol). The reaction became slightly homogeneous and then solid. The solid was heated to 125° C. for 24 h, showing a small amount of conversion. The reaction was heated to 135° C. for 3 days. The brown, homogeneous reaction was allowed to cool, and was diluted with 2N NaOH, water, and EtOAc. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting solid was adsorbed onto 2 g silica gel and purified by chromatography (0-100% 90/10 DCM/MeOH in DCM) to give N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4-(piperidin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyridazin-1-amine as an off-white solid. MS m/z=495 [M+H]+. Calc'd for C28H30N8O: 494.6.

Workup

  1. temperatureThe reaction was heated to 135° C. for 3 days
  2. customThe brown, homogeneous reaction
  3. temperatureto cool
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by chromatography (0-100% 90/10 DCM/MeOH in DCM)

Sources & evidence

ORD record
ord-8440f806399c4a29a69e8bd8300d9f73
Source dataset
uspto-grants-2011_09
Patent number
US08022221B2

Reaction notes

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