Sodium t-butoxide → Trifluoroacetic acid

HRID 713252Notes

Reaction equation

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

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 4-(2,4-difluorophenoxyl)piperidine hydrochloride (62.6 mg, 0.251 mmol), 6-benzyl-3-chloro-N-isopropyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine TFA salt (90 mg, 0.209 mmol), sodium tert-butoxide (60.2 mg, 0.627 mmol), BINAP (19.5 mg, 0.031 mmol) and Pd2(dba)3 (9.6 mg, 10.4 μmol) in toluene (1.04 mL) was heated at 100° C. for 16 h. The mixture was purified by HPLC Method A to afford 6-benzyl-3-(4-(2,4-difluorophenoxyl)piperidin-1-yl)-N-isopropyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine as its TFA salt (73.0 mg, 57.5%) as a yellow oil. ESI-MS m/z [M+H]+ 494.4.

Workup

customThe mixture was purified by HPLC Method A

Sources & evidence

ORD record: ord-9b620fa9af614f67877fcad9caf89540
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181249B2

Reaction notes

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