Sodium t-butoxide → Trifluoroacetic acid

HRID 713235Notes

Reaction equation

HRID 713235 reaction equation
Cl.[F:2][C:3]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:4]=1[O:5][CH:6]1[CH2:11][CH2:10][NH:9][CH2:8][CH2:7]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]3[CH2:45][CH2:44]3)[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:9]3[CH2:8][CH2:7][CH:6]([O:5][C:4]4[CH:12]=[CH:13][C:14]([O:16][CH3:17])=[CH:15][C:3]=4[F:2])[CH2:11][CH2:10]3)=[C:37]([NH:42][CH:43]3[CH2:44][CH2:45]3)[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 1181591584-(2-Fluoro-4-methoxyphenoxy)piperidine hydrochlorideHCID 1317340036-benzyl-3-chloro-N-cyclopropyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine TFA salt

Product 2

HCID 6422Trifluoroacetic acidYield 429.8%HCID 1181591976-benzyl-N-cyclopropyl-3-(4-(2-fluoro-4-methoxyphenoxy)piperidin-1-yl)-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
90 °C

Procedure

A mixture of 4-(2-fluoro-4-methoxyphenoxy)piperidine hydrochloride (73.2 mg, 0.280 mmol), 6-benzyl-3-chloro-N-cyclopropyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine TFA salt (100 mg, 0.233 mmol), sodium tert-butoxide (67.2 mg, 0.700 mmol), BINAP (21.8 mg, 0.035 mmol) and Pd2(dba)3 (10.7 mg, 0.012 mmol) in toluene (1.2 mL) 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 (114.2 mg, 97%) as a yellow foam. 1H NMR (400 MHz, methanol-d4) δ ppm 0.53-0.60 (m, 2H), 0.78-0.85 (m, 2H), 1.84-1.95 (m, 2H), 1.99-2.09 (m, 2H), 2.65-2.73 (m, 1H), 2.90-2.98 (m, 1H), 3.08-3.23 (m, 3H), 3.33-3.42 (m, 2H), 3.55-3.68 (m, 2H), 3.75 (s, 3H), 4.16-4.24 (m, 1H), 4.28-4.40 (m, 2H), 4.50-4.59 (m, 2H), 6.67 (s, 1H), 6.73 (dd, J=12.9, 3.0 Hz, 1H), 7.01-7.09 (m, 1H), 7.52-7.61 (m, 5H); ESI-MS m/z [M+H]+ 504.4.

Workup

  1. customThe mixture was directly purified by HPLC Method A

Sources & evidence

ORD record
ord-49b73cf4e3c14fdd86bda6260e08e20a
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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