Cyclobutylamine → Trifluoroacetic acid

HRID 713223Notes

Reaction equation

[CH:1]1([NH2:5])[CH2:4][CH2:3][CH2:2]1.[OH:6][C:7]([C:9]([F:12])([F:11])[F:10])=[O:8].[CH2:13]([N:20]1[CH2:29][CH2:28][C:27]2[C:22](=[N:23][C:24](Cl)=[C:25]([N:30]3[CH2:35][CH2:34][CH:33]([O:36][C:37]4[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][C:38]=4[F:45])[CH2:32][CH2:31]3)[N:26]=2)[CH2:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=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>[CH2:13]([N:20]1[CH2:29][CH2:28][C:27]2[C:22](=[N:23][C:24]([NH:5][CH:1]3[CH2:4][CH2:3][CH2:2]3)=[C:25]([N:30]3[CH2:31][CH2:32][CH:33]([O:36][C:37]4[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][C:38]=4[F:45])[CH2:34][CH2:35]3)[N:26]=2)[CH2:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[C:7]([OH:8])([C:9]([F:12])([F:11])[F:10])=[O:6]

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of cyclobutanamine (49.9 μL, 0.584 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 (116.2 mg, 0.195 mmol), sodium tert-butoxide (56.1 mg, 0.584 mmol), BINAP (18.2 mg, 0.029 mmol) and Pd2(dba)3 (26.7 mg, 0.029 mmol) in toluene (649 μL) was heated at 90° C. in a sealed tube for 16 h. The mixture was directly purified by HPLC Method A to afford 6-benzyl-N-cyclobutyl-2-(4-(2-fluoro-4-methoxyphenoxy)piperidin-1-yl)-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-3-amine as its TFA salt (103.4 mg, 84%) as a yellow foam. ESI-MS m/z [M+H]+ 518.4

Workup

customThe mixture was directly purified by HPLC Method A

Sources & evidence

ORD record: ord-4ab3ebca3d6c40249b3c791a862d2ba2
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181249B2

Reaction notes

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