Methyl 4-amino-2-fluorobenzoate → HCID 18452517, compound

HRID 1271066Notes

Reaction equation

HRID 1271066 reaction equation
C([O:4][C:5]1[CH:10]=[C:9]([F:11])[C:8]([F:12])=[CH:7][C:6]=1[C:13](Cl)=[O:14])(=O)C.[CH3:16][O:17][C:18](=[O:27])[C:19]1[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][C:20]=1[F:26]>>[F:11][C:9]1[C:8]([F:12])=[CH:7][C:6]([C:13]([NH:25][C:22]2[CH:23]=[CH:24][C:19]([C:18]([O:17][CH3:16])=[O:27])=[C:20]([F:26])[CH:21]=2)=[O:14])=[C:5]([OH:4])[CH:10]=1

Participants

3

Reactant 2

HCID 21957875Methyl 4-amino-2-fluorobenzoateHCID 59556245HCID 59556245, compound

Product 1

HCID 18452517HCID 18452517, compoundYield 67.3%

Procedure

Analogous to the method described in Ex 1, 2-(chlorocarbonyl)-4,5-difluorophenyl acetate (0.2 g, 0.85 mmol) and methyl-2-fluoro-4-aminobenzoate (0.174 g, 1.1 mmol) were coupled to yield methyl 4-(4,5-difluoro-2-hydroxybenzamido)-2-fluorobenzoate (0.186 g, 64%). RP-HPLC: 2.61 min; ES-MS (M+H)+=326.0. This intermediate was cyclized with formaldehyde, followed by displacement of 7-fluoro with methylamine analogues to method above to give methyl 4-(6-fluoro-7-methylamino-4-oxo-2H-benzo[e][1,3]oxazin-3(4H)benzoate. The methyl ester was hydrolyzed as described in Ex. 55 and then which was coupled with 5-chlorothiophene-2-sulfonamide as described in Ex. 56. The solvent was removed and the product purified on HPLC (C18) to give N-(5-chlorothiophen-2-ylsulfonyl)2-fluoro-4-(6-fluoro-7-(methylamino)-4-oxo-2H-benzo[e] [1,3] oxazin-3(4H)-yl) benzamide (0.005 g, 15%). RP-HPLC: 2.78 min; ES-MS (M+H)+=514; 1H-NMR (MeOH-d4) δ (ppm): 2.8 (s, 3), 5.6 (s, 2), 6.2 (d, 1), 7.1 (d, 1), 7.3 (d, 1), 7.4 (dd, 1), 7.5 (dd, 1), 7.7 (dd, 1), 7.9 (dd, 1).

Sources & evidence

ORD record
ord-84b8830e54e1418f996b85fcd61ae7f5
Source dataset
uspto-grants-2007_04
Patent number
US07205296B2

Reaction notes

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