Formaldehyde → Trifluoroacetic acid

HRID 713320Notes

Reaction equation

HRID 713320 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].[Cl:18][C:19]1[CH:20]=[CH:21][C:22]([F:47])=[C:23]([C:25]([CH:27]2[CH2:32][CH2:31][N:30]([C:33]3[N:38]=[C:37]4[CH2:39][NH:40][CH2:41][CH2:42][C:36]4=[N:35][C:34]=3[NH:43][CH:44]([CH3:46])[CH3:45])[CH2:29][CH2:28]2)=[O:26])[CH:24]=1.C=O>CO>[Cl:18][C:19]1[CH:20]=[CH:21][C:22]([F:47])=[C:23]([C:25]([CH:27]2[CH2:32][CH2:31][N:30]([C:33]3[N:38]=[C:37]4[CH2:39][N:40]([CH3:2])[CH2:41][CH2:42][C:36]4=[N:35][C:34]=3[NH:43][CH:44]([CH3:45])[CH3:46])[CH2:29][CH2:28]2)=[O:26])[CH:24]=1.[C:12]([OH:13])([C:14]([F:17])([F:16])[F:15])=[O:11]

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 81531DiisopropylethylamineHCID 5360545SodiumHCID 131734037HCID 131734037, compound

Product 2

HCID 6422Trifluoroacetic acidYield 120.6%HCID 118159276HCID 118159276, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Sodium triacetoxyhydroborate (6.9 mg, 0.033 mmol) was added to a solution of DIPEA (6 μL, 0.033 mmol), (5-chloro-2-fluorophenyl)(1-(2-(isopropylamino)-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-3-yl)piperidin-4-yl)methanone TFA salt (8.9 mg, 0.016 mmol) and formaldehyde (1.5 μL, 0.016 mmol) in MeOH (160 μL) at rt. After 30 min, the mixture was purified by HPLC Method A to give the title compound as a TFA salt (2.2 mg, 24.1%) as a yellow film. 1H NMR (400 MHz, methanol-d4) δ ppm 1.24 (d, J=6.6 Hz, 6H), 1.81-1.94 (m, 2H), 1.96-2.05 (m, 2H), 2.85 (t, J=11.5 Hz, 2H), 3.00 (d, J=6.3 Hz, 2H), 3.07 (s, 3H), 3.44-3.53 (m, 4H), 3.71-3.82 (m, 1H), 4.14-4.23 (m, 2H), 4.28-4.37 (m, 1H), 7.28 (dd, J=10.6, 8.8 Hz, 1H), 7.61 (ddd, J=8.8, 4.1, 2.8 Hz, 1H), 7.75 (dd, J=6.1, 2.8 Hz, 1H); ESI-MS m/z [M+H]+ 446.3.

Workup

  1. customthe mixture was purified by HPLC Method A

Sources & evidence

ORD record
ord-eaee889b9fc241389afcade9fbe9bd33
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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