Formaldehyde → Trifluoroacetic acid

HRID 713342Notes

Reaction equation

HRID 713342 reaction equation
[OH:1][C:2]([C:4]([F:7])([F:6])[F:5])=[O:3].[CH:8]1([NH:11][C:12]2[N:13]=[C:14]3[CH2:36][CH2:35][NH:34][CH:33]([CH3:37])[C:15]3=[N:16][C:17]=2[N:18]2[CH2:23][CH2:22][CH:21]([O:24][C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=3[F:32])[CH2:20][CH2:19]2)[CH2:10][CH2:9]1.C=O.CCN(C(C)C)C(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH:8]1([NH:11][C:12]2[N:13]=[C:14]3[CH2:36][CH2:35][N:34]([CH3:2])[CH:33]([CH3:37])[C:15]3=[N:16][C:17]=2[N:18]2[CH2:19][CH2:20][CH:21]([O:24][C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=3[F:32])[CH2:22][CH2:23]2)[CH2:10][CH2:9]1.[C:2]([OH:3])([C:4]([F:7])([F:6])[F:5])=[O:1]

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 131734042HCID 131734042, compound

Product 2

HCID 6422Trifluoroacetic acidYield 250.6%HCID 118159141HCID 118159141, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of N-cyclopropyl-3-(4-(2,4-difluorophenoxyl)piperidin-1-yl)-5-methyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine TFA salt (15 mg, 0.028 mmol), formaldehyde (1.5 μL, 0.057 mmol), and DIPEA (5.0 μL, 0.028 mmol) in DCM (283 μL) was stirred for 10 min. To this was then added sodium triacetoxyborohydride (18.0 mg, 0.085 mmol) and the reaction mixture was stirred overnight. Purification by HPLC Method A afforded the title compound as a TFA salt (4 mg). 1H NMR (400 MHz, methanol-d4) 6 ppm 0.60-0.67 (m, 2H), 0.83-0.92 (m, 2H), 1.64-1.80 (m, 3H), 1.87-2.04 (m, 2H), 2.05-2.21 (m, 2H), 2.74 (tt, J=7.0, 3.6 Hz, 1H), 2.98-3.21 (m, 7H), 3.35-3.51 (m, 2H), 3.59 (d, J=6.6 Hz, 1H), 3.78 (br s, 1H), 4.42 (br s, 1H), 4.49 (td, J=7.4, 3.7 Hz, 1H), 6.86-6.93 (m, 1H), 6.96-7.05 (m, 1H), 7.18 (td, J=9.2, 5.3 Hz, 1H).

Workup

  1. customPurification by HPLC Method A

Sources & evidence

ORD record
ord-686ad5cd7f2f4df998e6d712d845d08f
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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