Formaldehyde → Trifluoroacetic acid

HRID 713323Notes

Reaction equation

HRID 713323 reaction equation
[Na].[CH3:2]CN(C(C)C)C(C)C.[OH:11][C:12]([C:14]([F:17])([F:16])[F:15])=[O:13].[F:18][C:19]1[CH:45]=[C:44]([F:46])[CH:43]=[CH:42][C:20]=1[O:21][CH:22]1[CH2:27][CH2:26][N:25]([C:28]2[N:33]=[C:32]3[CH2:34][NH:35][CH2:36][CH2:37][C:31]3=[N:30][C:29]=2[NH:38][CH:39]([CH3:41])[CH3:40])[CH2:24][CH2:23]1.C=O>CO>[F:18][C:19]1[CH:45]=[C:44]([F:46])[CH:43]=[CH:42][C:20]=1[O:21][CH:22]1[CH2:23][CH2:24][N:25]([C:28]2[N:33]=[C:32]3[CH2:34][N:35]([CH3:2])[CH2:36][CH2:37][C:31]3=[N:30][C:29]=2[NH:38][CH:39]([CH3:41])[CH3:40])[CH2:26][CH2:27]1.[C:12]([OH:13])([C:14]([F:17])([F:16])[F:15])=[O:11]

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 81531DiisopropylethylamineHCID 5360545SodiumHCID 1317340273-(4-(2,4-difluorophenoxy)piperidin-1-yl)-N-isopropyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine TFA salt

Product 2

HCID 6422Trifluoroacetic acidYield 372%HCID 1181593523-(4-(2,4-difluorophenoxy)piperidin-1-yl)-N-isopropyl-6-methyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Sodium triacetoxyhydroborate (12.3 mg, 0.058 mmol) was added to a solution of DIPEA (10 μL, 0.058 mmol), 3-(4-(2,4-difluorophenoxyl)piperidin-1-yl)-N-isopropyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine TFA salt (15.0 mg, 0.029 mmol) and formaldehyde (2 μL, 0.029 mmol) in MeOH (290 μL) at rt. After 30 min, the mixture was purified by HPLC Method A to give the title compound as a TFA salt (12.3 mg, 80%) as a yellow film. 1H NMR (400 MHz, methanol-d4) δ ppm 1.25 (d, J=6.6 Hz, 6H), 1.90-2.00 (m, 2H), 2.07-2.16 (m, 2H), 2.96-3.05 (m, 3H), 3.08 (br s, 4H), 3.33-3.42 (m, 2H), 3.43-3.85 (m, 2H), 4.14-4.38 (m, 3H), 4.44-4.51 (m, 1H), 6.84-6.91 (m, 1H), 6.95-7.02 (m, 1H), 7.17 (td, J=9.2, 5.6 Hz, 1H); ESI-MS m/z [M+H]+ 418.3.

Workup

  1. customthe mixture was purified by HPLC Method A

Sources & evidence

ORD record
ord-7edd25a07a174d8ca97c7b05f9bba22f
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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