Cyclopropylamine → Trifluoroacetic acid

HRID 713312Notes

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

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of cyclopropanamine (13.6 mg, 0.237 mmol), 3-chloro-2-(4-(2-fluoro-4-methoxyphenoxy)piperidin-1-yl)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazine TFA salt (30.9 mg, 0.059 mmol), sodium tert-butoxide (11.4 mg, 0.119 mmol), BINAP (5.5 mg, 8.90 μmol) and Pd2(dba)3 (2.7 mg, 2.97 μmol) in toluene (200 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 (12.9 mg, 40.2%) as a yellow film. 1H NMR (400 MHz, methanol-d4) δ ppm 0.53-0.58 (m, 2H), 0.75-0.81 (m, 2H), 1.86-1.96 (m, 2H), 2.02-2.12 (m, 2H), 2.64-2.70 (m, 1H), 2.94-3.02 (m, 1H), 3.08-3.12 (m, 3H), 3.17-3.27 (m, 3H), 3.34-3.42 (m, 2H), 3.59-3.68 (m, 2H), 3.75 (s, 3H), 4.25-4.41 (m, 3H), 6.64-6.69 (m, 1H), 6.70-6.76 (m, 1H), 7.03-7.10 (m, 1H); ESI-MS m/z [M+H]+ 428.4.

Workup

customThe mixture was directly purified by HPLC Method A

Sources & evidence

ORD record: ord-af2aea7bd35c4fbf85cf6cbd2697b6c0
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181249B2

Reaction notes

Loading…