Isopropylamine → HCID 118159249, compound

HRID 713221Notes

Reaction equation

HRID 713221 reaction equation
OC(C(F)(F)F)=O.[CH2:8]([N:15]1[CH2:24][CH2:23][C:22]2[C:17](=[N:18][C:19](Cl)=[C:20]([N:25]3[CH2:30][CH2:29][CH:28]([O:31][C:32]4[CH:39]=[CH:38][C:35]([C:36]#[N:37])=[CH:34][C:33]=4[F:40])[CH2:27][CH2:26]3)[N:21]=2)[CH2:16]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[CH3:42][CH:43]([NH2:45])[CH3:44].CC(C)([O-])C.[Na+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:8]([N:15]1[CH2:24][CH2:23][C:22]2[C:17](=[N:18][C:19]([NH:45][CH:43]([CH3:44])[CH3:42])=[C:20]([N:25]3[CH2:30][CH2:29][CH:28]([O:31][C:32]4[CH:39]=[CH:38][C:35]([C:36]#[N:37])=[CH:34][C:33]=4[F:40])[CH2:27][CH2:26]3)[N:21]=2)[CH2:16]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

7

Reactant 4

HCID 6363IsopropylamineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 131733995HCID 131733995, compound

Product 1

HCID 118159249HCID 118159249, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 4-((1-(6-benzyl-3-chloro-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-yl)piperidin-4-yl)oxy)-3-fluorobenzonitrile TFA salt (213.9 mg, 0.361 mmol) in toluene (1.44 mL) was treated with propan-2-amine (0.118 mL, 1.445 mmol), sodium tert-butoxide (69.4 mg, 0.723 mmol), BINAP (22.5 mg, 0.036 mmol), and Pd2(dba)3 (16.5 mg, 0.018 mmol). Nitrogen gas was bubbled through the solution for 5 min. The reaction mixture was then sealed and the reaction mixture was heated to 90° C. overnight. The reaction mixture was allowed to cool to room temperature. Solvent was removed under reduced pressure and the residue was purified by HPLC Method B, with the exception that a Waters SunFire™ C18, 5 μm, ID 30×75 mm column was used, using a 40% to 70% ACN gradient to give the title compound, as a TFA salt, as a yellow oil (105 mg, 47.3%). ESI-MS m/z [M+H]+ 501.5.

Workup

  1. customNitrogen gas was bubbled through the solution for 5 min
  2. customThe reaction mixture was then sealed
  3. temperatureto cool to room temperature
  4. customSolvent was removed under reduced pressure
  5. customthe residue was purified by HPLC Method B, with the exception that a Waters SunFire™ C18, 5 μm, ID 30×75 mm column

Sources & evidence

ORD record
ord-746aaa20e8344151b0e7e313c144e092
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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