Isopropylamine → Trifluoroacetic acid

HRID 713244Notes

Reaction equation

HRID 713244 reaction equation
[CH3:1][CH:2]([NH2:4])[CH3:3].[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:2]([CH3:3])[CH3:1])=[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.[C:6]([OH:7])([C:8]([F:11])([F:10])[F:9])=[O:5]

Participants

8

Reactant 3

HCID 6363IsopropylamineHCID 23676156Sodium t-butoxideHCID 131733997HCID 131733997, compound

Product 2

HCID 6422Trifluoroacetic acidYield 231.8%HCID 118159365HCID 118159365, compound

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

A mixture of propan-2-amine (71 μL, 0.827 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 (123.4 mg, 0.207 mmol), sodium tert-butoxide (39.7 mg, 0.413 mmol), BINAP (19.3 mg, 0.031 mmol) and Pd2(dba)3 (9.5 mg, 10.33 μmol) in toluene (690 μL) was heated at 100° C. for 16 h. The mixture was then purified by HPLC Method A to give the title compound as a TFA salt (54.7 mg, 42.7%) as a yellow film. 1H NMR (400 MHz, methanol-d4) δ ppm 1.22 (d, J=6.6 Hz, 6H), 1.87-2.13 (m, 4H), 2.94-3.10 (m, 4H), 3.35-3.53 (m, 3H), 3.75 (s, 3H), 3.79-3.88 (m, 1H), 4.07-4.27 (m, 3H), 4.31-4.39 (m, 1H), 4.52 (br s, 2H), 6.66 (ddd, J=8.9, 3.0, 1.5 Hz, 1H), 6.73 (dd, J=12.9, 3.0 Hz, 1H), 7.03-7.10 (m, 1H), 7.51-7.60 (m, 5H); ESI-MS m/z [M+H]+ 506.4.

Workup

  1. customThe mixture was then purified by HPLC Method A

Sources & evidence

ORD record
ord-86e89c06e596472882bc52018f36ba9e
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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