Sodium t-butoxide → Trifluoroacetic acid

HRID 713241Notes

Reaction equation

HRID 713241 reaction equation
Cl.[F:2][C:3]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:4]=1[CH:10]([F:17])[CH:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.[OH:18][C:19]([C:21]([F:24])([F:23])[F:22])=[O:20].[CH2:25]([N:32]1[CH2:41][CH2:40][C:39]2[C:34](=[N:35][C:36](Cl)=[C:37]([NH:42][CH:43]([CH3:45])[CH3:44])[N:38]=2)[CH2:33]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=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>[CH2:25]([N:32]1[CH2:41][CH2:40][C:39]2[C:34](=[N:35][C:36]([N:14]3[CH2:15][CH2:16][CH:11]([CH:10]([C:4]4[CH:5]=[CH:6][C:7]([F:9])=[CH:8][C:3]=4[F:2])[F:17])[CH2:12][CH2:13]3)=[C:37]([NH:42][CH:43]([CH3:45])[CH3:44])[N:38]=2)[CH2:33]1)[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1.[C:19]([OH:20])([C:21]([F:24])([F:23])[F:22])=[O:18]

Participants

8

Reactant 3

HCID 23676156Sodium t-butoxideHCID 900390154-((2,4-Difluorophenyl)fluoromethyl)piperidine hydrochlorideHCID 1317340076-benzyl-3-chloro-N-isopropyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine TFA salt

Product 2

HCID 6422Trifluoroacetic acidYield 409.4%HCID 1181593706-benzyl-3-(4-((2,4-difluorophenyl)fluoromethyl)piperidin-1-yl)-N-isopropyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

A mixture of 4-((2,4-difluorophenyl)fluoromethyl)piperidine hydrochloride (74.0 mg, 0.279 mmol), 6-benzyl-3-chloro-N-isopropyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine TFA salt (100 mg, 0.232 mmol), sodium tert-butoxide (66.9 mg, 0.696 mmol), BINAP (21.7 mg, 0.035 mmol) and Pd2(dba)3 (10.6 mg, 0.012 mmol) in toluene (1.2 mL) was heated at 100° C. in a sealed tube for 14 h. The mixture was purified by HPLC Method A to give the title compound as a TFA salt (108.3 mg, 74.8%) as a yellow solid. 1H NMR (400 MHz, methanol-d4) δ ppm 1.23 (dd, J=6.4, 2.4 Hz, 6H), 1.39-1.47 (m, 1H), 1.51-1.72 (m, 2H), 1.95-2.12 (m, 2H), 2.58-2.70 (m, 2H), 3.04 (br s, 2H), 3.36-3.83 (m, 4H), 4.09-4.21 (m, 3H), 4.51 (br s, 2H), 5.52 (dd, J=46.2, 7.3 Hz, 1H), 6.97-7.07 (m, 2H), 7.45-7.59 (m, 6H); ESI-MS m/z [M+H]+ 510.4.

Workup

  1. customThe mixture was purified by HPLC Method A

Sources & evidence

ORD record
ord-1782f77051c043fc9c62083ef03c7273
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

Loading…