Cyclopropylamine → Trifluoroacetic acid

HRID 713236Notes

Reaction equation

HRID 713236 reaction equation
[CH:1]1([NH2:4])[CH2:3][CH2:2]1.[OH:5][C:6]([C:8]([F:11])([F:10])[F:9])=[O:7].[CH2:12]([N:19]1[CH2:28][CH2:27][C:26]2[C:21](=[N:22][C:23](Cl)=[C:24]([N:29]3[CH2:34][CH2:33][CH:32]([O:35][C:36]4[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][C:37]=4[F:44])[CH2:31][CH2:30]3)[N:25]=2)[CH2:20]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.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>[CH2:12]([N:19]1[CH2:28][CH2:27][C:26]2[C:21](=[N:22][C:23]([NH:4][CH:1]3[CH2:3][CH2:2]3)=[C:24]([N:29]3[CH2:30][CH2:31][CH:32]([O:35][C:36]4[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][C:37]=4[F:44])[CH2:33][CH2:34]3)[N:25]=2)[CH2:20]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[C:6]([OH:7])([C:8]([F:11])([F:10])[F:9])=[O:5]

Participants

8

Reactant 3

HCID 69828CyclopropylamineHCID 23676156Sodium t-butoxideHCID 131733997HCID 131733997, compound

Product 2

HCID 6422Trifluoroacetic acidYield 362.6%HCID 118159286HCID 118159286, compound

Reagents, catalysts & solvents 3

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

Conditions

Temperature
90 °C

Procedure

A mixture of cyclopropanamine (27.2 mg, 0.477 mmol), 6-benzyl-3-chloro-2-(4-(2-fluoro-4-methoxyphenoxy)piperidin-1-yl)-5,6,7,8-tetrahydropyrido[3,4-b]pyrazine TFA salt (71.2 mg, 0.119 mmol), sodium tert-butoxide (22.9 mg, 0.239 mmol), BINAP (11.1 mg, 0.018 mmol) and Pd2(dba)3 (5.5 mg, 5.96 μmol) in toluene (400 μL) was heated at 90° C. for 14 h. The mixture was directly purified by HPLC Method A to give the title compound as a TFA salt (49.2 mg, 66.8%) as a yellow solid. 1H NMR (400 MHz, methanol-d4) δ ppm 0.50-0.55 (m, 2H), 0.76 (dd, J=7.0, 1.9 Hz, 2H), 1.86-1.96 (m, 2H), 2.01-2.10 (m, 2H), 2.63 (tt, J=7.0, 3.6 Hz, 1H), 2.93-3.01 (m, 2H), 3.07 (br s, 2H), 3.34-3.41 (m, 2H), 3.56 (br s, 2H), 3.75 (s, 3H), 4.23 (br s, 2H), 4.30-4.37 (m, 1H), 4.53 (br s, 2H) 6.63-6.68 (m, 1H), 6.73 (dd, J=12.8, 2.9 Hz, 1H), 7.05 (t, J=9.2 Hz, 1H), 7.52-7.61 (m, 5H); ESI-MS m/z [M+H]+ 504.4.

Workup

  1. customThe mixture was directly purified by HPLC Method A

Sources & evidence

ORD record
ord-565a6008e7d44cf395f3625f2ec36ce3
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

Loading…