Formaldehyde → Trifluoroacetic acid

HRID 2067897Notes

Reaction equation

HRID 2067897 reaction equation
[F:1][CH:2]([F:37])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[N:12][C:13]([NH:16][C:17]3[CH:18]=[CH:19][C:20]([CH3:36])=[C:21]([NH:23][C:24]([N:26]4[CH2:31][CH2:30][NH:29][CH:28]([C:32]([F:35])([F:34])[F:33])[CH2:27]4)=[O:25])[CH:22]=3)=[N:14][CH:15]=2)=[CH:6][CH:5]=1.[CH2:38]=[O:39].[O-:40]S([O-])(=O)=O.[Na+].[Na+]>C(Cl)Cl>[F:37][CH:2]([F:1])[O:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]2[CH:11]=[N:12][C:13]([NH:16][C:17]3[CH:18]=[CH:19][C:20]([CH3:36])=[C:21]([NH:23][C:24]([N:26]4[CH2:31][CH2:30][N:29]([CH3:38])[CH:28]([C:32]([F:35])([F:34])[F:33])[CH2:27]4)=[O:25])[CH:22]=3)=[N:14][CH:15]=2)=[CH:8][CH:9]=1.[C:38]([OH:40])([C:32]([F:35])([F:34])[F:33])=[O:39]

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 24436Sodium SulfateHCID 58542195N-(5-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)-2-methylphenyl)-3-(trifluoromethyl)piperazine-1-carboxamide

Product 2

HCID 6422Trifluoroacetic acidHCID 25196951N-(5-(5-(4-(Difluoromethoxy)phenyl)pyrimidin-2-ylamino)-2-methylphenyl)-3-(trifluoromethyl)-4-methylpiperazine-1-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of N-(5-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)-2-methylphenyl)-3-(trifluoromethyl)piperazine-1-carboxamide D11 (0.05 mmol), HCHO (0.15 mmol, 30% aqueous) and anhydrous Na2SO4 (1.5 mmol) in DCM (2 mL) is stirred at rt for 30 min. Then NaHB(OAc)3 (0.3 mmol) is added and the resulting mixture is stirred for 12 h. Purification by prep-HPLC (ACN gradient 10-70%) affords N-(5-(5-(4-(Difluoromethoxy)phenyl)pyrimidin-2-ylamino)-2-methylphenyl)-3-(trifluoromethyl)-4-methylpiperazine-1-carboxamide D12 as a TFA salt. 1H NMR (400 MHz, d6-DMSO) δ 9.69 (s, 1H), 8.80 (s, 2H), 8.15 (s, 1H), 7.76 (d, J=8.8 Hz, 2H), 7.61 (s, 1H), 7.50 (d, J=8.0 Hz, 1H), 7.28 (t, J=74.0 Hz, 1H), 7.27 (d, J=8.8 Hz, 2H), 7.09 (d, J=8.4 Hz, 1H), 3.68 (m, 1H), 3.54 (m, 1H), 2.88 (m, 1H), 2.51 (m, 4H), 2.47 (s, 1H), 2.09 (s, 3H). MS (m/z) (M+1)+: 537.2.

Workup

  1. customPurification by prep-HPLC (ACN gradient 10-70%)

Sources & evidence

ORD record
ord-fc40094233ae45858407ed95ec5028a5
Source dataset
uspto-grants-2012_10
Patent number
US08293757B2

Reaction notes

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