Isopropylamine → Trifluoroacetic acid

HRID 713225Notes

Reaction equation

HRID 713225 reaction equation
[OH:1][C:2]([C:4]([F:7])([F:6])[F:5])=[O:3].[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:37]=[CH:36][C:35]([F:38])=[CH:34][C:33]=4[F:39])[CH2:27][CH2:26]3)[N:21]=2)[CH:16]1[CH3:41])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[CH:42]([NH2:45])([CH3:44])[CH3:43].CC(C)([O-])C.[Na+]>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].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>[CH2:8]([N:15]1[CH2:24][CH2:23][C:22]2[C:17](=[N:18][C:19]([NH:45][CH:42]([CH3:44])[CH3:43])=[C:20]([N:25]3[CH2:30][CH2:29][CH:28]([O:31][C:32]4[CH:37]=[CH:36][C:35]([F:38])=[CH:34][C:33]=4[F:39])[CH2:27][CH2:26]3)[N:21]=2)[CH:16]1[CH3:41])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[C:2]([OH:3])([C:4]([F:7])([F:6])[F:5])=[O:1]

Participants

8

Reactant 3

HCID 6363IsopropylamineHCID 23676156Sodium t-butoxideHCID 131733999HCID 131733999, compound

Product 2

HCID 6422Trifluoroacetic acidYield 328.6%HCID 118159120HCID 118159120, compound

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

Combined 6-benzyl-3-chloro-2-(4-(2,4-difluorophenoxyl)piperidin-1-yl)-5-methyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazine TFA salt (280 mg, 0.467 mmol), isopropylamine (200 μL, 2.337 mmol), Pd2(dba)3 (42.8 mg, 0.047 mmol), BINAP (58.2 mg, 0.093 mmol), and sodium tert-butoxide (112 mg, 1.169 mmol) in toluene (2.34 mL) and heated at 100° C. for 30 min under microwave conditions. The reaction mixture was cooled, concentrated in vacuo, and purified by HPLC Method A to give 6-benzyl-2-(4-(2,4-difluorophenoxyl)piperidin-1-yl)-N-isopropyl-5-methyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-3-amine as a TFA salt (175 mg) as a brown oil.

Workup

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated in vacuo
  3. custompurified by HPLC Method A

Sources & evidence

ORD record
ord-8a5b836b88434d4195a3bfe0aca7300a
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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