Dimethylformamide → (S)-N2-((3-Fluoropyridin-2-yl)(4-(trifluoromethyl)phenyl)-methyl)-N5-methylpyridine-2,5-dicarboxamide 2,2,2-trifluoroacetate

HRID 2370794

Reaction equation

HRID 2370794 reaction equation
[F:1][C:2]1[C:3]([C@@H:8]([NH:19][C:20]([C:22]2[CH:30]=[CH:29][C:25]([C:26]([OH:28])=O)=[CH:24][N:23]=2)=[O:21])[C:9]2[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=2)=[N:4][CH:5]=[CH:6][CH:7]=1.C[CH2:32][N:33](C(C)C)C(C)C.CN.CN(C([O:49]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN([CH:69]=[O:70])C>>[F:16][C:15]([F:18])([F:17])[C:69]([OH:70])=[O:49].[F:1][C:2]1[C:3]([C@H:8]([C:9]2[CH:10]=[CH:11][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:13][CH:14]=2)[NH:19][C:20]([C:22]2[CH:30]=[CH:29][C:25]([C:26]([NH:33][CH3:32])=[O:28])=[CH:24][N:23]=2)=[O:21])=[N:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 6329MethylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 71144036(S)-6-(((3-Fluoropyridin-2-yl)(4-(trifluoromethyl)phenyl)-methyl)carbamoyl)nicotinic Acid

Product 1

HCID 86687970(S)-N2-((3-Fluoropyridin-2-yl)(4-(trifluoromethyl)phenyl)-methyl)-N5-methylpyridine-2,5-dicarboxamide 2,2,2-trifluoroacetate

Conditions

Temperature
23 °C

Procedure

To a 50 mL round bottom flask containing (S)-6-(((3-fluoropyridin-2-yl)-(4-(trifluoromethyl)phenyl)methyl)carbamoyl)nicotinic acid (Example 280) (86 mg, 0.205 mmol) was added DMF (3 mL). The resulting mixture was stirred at 23° C. for 2 min. At this time, DIPEA (143 μL, 0.820 mmol), methylamine (2.0 M in THF, 103 μL, 0.205 mmol) and then HATU (78 mg, 0.205 mmol) were added to the flask. The reaction was stirred for 1 h and then directly purified by reverse phase HPLC. The pure fractions were concentrated to give the title compound as a white solid. 1H NMR (300 MHz, CDCl3) δ ppm 9.85 (d, J=7.2 Hz, 1H), 9.00 (s, 1H), 8.55 (d, J=4.4 Hz, 1H), 8.20 (s, 2H), 7.60 (s, 4H), 7.52 (t, J=8.7 Hz, 1H), 7.45-7.34 (m, 1H), 6.74 (d, J=7.3 Hz, 1H), 6.55 (br. s., 1H), 3.07 (d, J=4.5 Hz, 3H). MS (ESI pos. ion) m/z: 433.1 (M+H).

Workup

  1. stirringThe reaction was stirred for 1 h
  2. customdirectly purified by reverse phase HPLC
  3. concentrationThe pure fractions were concentrated

Sources & evidence

ORD record
ord-72f637184c9342449c90818546b67b6f
Source dataset
uspto-grants-2014_04
Patent number
US08710043B2

Linked notes

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