Formaldehyde → Trifluoroacetic acid

HRID 15522Notes

Reaction equation

HRID 15522 reaction equation
[OH:1][C:2]([C:4]([F:7])([F:6])[F:5])=[O:3].[F:8][C:9]1[CH:10]=[C:11]([NH:36][C:37]([C:39]2[C:40](=[O:52])[N:41]([C:45]3[CH:50]=[CH:49][C:48]([F:51])=[CH:47][CH:46]=3)[CH:42]=[CH:43][CH:44]=2)=[O:38])[CH:12]=[CH:13][C:14]=1[O:15][C:16]1[C:25]2[C:20](=[CH:21][C:22]([O:28][CH2:29][CH:30]3[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]3)=[C:23]([O:26][CH3:27])[CH:24]=2)[N:19]=[CH:18][CH:17]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C=O>C(Cl)Cl>[F:8][C:9]1[CH:10]=[C:11]([NH:36][C:37]([C:39]2[C:40](=[O:52])[N:41]([C:45]3[CH:46]=[CH:47][C:48]([F:51])=[CH:49][CH:50]=3)[CH:42]=[CH:43][CH:44]=2)=[O:38])[CH:12]=[CH:13][C:14]=1[O:15][C:16]1[C:25]2[C:20](=[CH:21][C:22]([O:28][CH2:29][CH:30]3[CH2:35][CH2:34][N:33]([CH3:2])[CH2:32][CH2:31]3)=[C:23]([O:26][CH3:27])[CH:24]=2)[N:19]=[CH:18][CH:17]=1.[C:2]([OH:3])([C:4]([F:7])([F:6])[F:5])=[O:1]

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 86611353HCID 86611353, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 16226147N-(3-Fluoro-4-(6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinolin-4-yloxy)phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of N-(3-fluoro-4-(6-methoxy-7-(piperidin-4-ylmethoxy)quinolin-4-yloxy)phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide TFA salt (22 mg, 0.030 mmol) and NaBH(OAc)3 (40 mg) in CH2Cl2 was added HCHO (0.1 mL of 33% solution) and the reaction mixture was stirred at rt for 6 h. Direct purification by preparative HPLC afforded the desired product as a white TFA salt solid (11 mg, 50%). 1H NMR (CDCl3) δ 12.16 (s, 1H), 8.77 (dd, 1H, J=7.7, 2.2 Hz), 8.55 (d, 1H, J=6.1 Hz), 8.08 (d, 1H, J=1.6 Hz), 8.06 (dd, 1H, J= 12.1, 1.6 Hz), 7.64-7.27 (m, 8H), 6.71 (d, 1H, J=6.6 Hz), 6.66 (t, 1H, J=6.6 Hz), 4.27 (d, 2H, J=5.5 Hz), 4.07 (s, 3H), 3.66 (d, 2H, J=12.1 Hz), 2.81 (s, 3H), 2.87-1.97 (m, 7H); MS(ESI+) m/z 627.4 (M+H)+.

Workup

  1. customDirect purification by preparative HPLC

Sources & evidence

ORD record
ord-289c213386154e39a7f09e168ec7a9d8
Source dataset
uspto-grants-2010_06
Patent number
US07732613B2

Reaction notes

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