4-Methylmorpholine → HCID 77845375, compound

HRID 1484178Notes

Reaction equation

HRID 1484178 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([O:10]C)=[O:9])=[N:6][CH:7]=1.[F:12][C:13]1[CH:32]=[CH:31][C:16]([O:17][C:18]2[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:23][C:19]=2[C:20](O)=[O:21])=[CH:15][CH:14]=1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[OH-].[Na+]>CN(C=O)C.CO>[F:12][C:13]1[CH:32]=[CH:31][C:16]([O:17][C:18]2[CH:26]=[C:25]([C:27]([F:28])([F:29])[F:30])[CH:24]=[CH:23][C:19]=2[C:20]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]([OH:10])=[O:9])=[N:6][CH:7]=2)=[O:21])=[CH:15][CH:14]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 14798Sodium HydroxideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 12457877Methyl 5-aminopyridine-2-carboxylateHCID 90314056HCID 90314056, compound

Product 1

HCID 77845375HCID 77845375, compoundYield 33%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

A solution of methyl 5-aminopicolinate (15.2 mg, 0.1 mmol), 2-(4-fluorophenoxy)-4-(trifluoromethyl)benzoic acid (33.0 mg, 0.12 mmol), N-methylmorpholine (22 μL, 0.2 mmol) and HATU (45.6 mg, 0.12 mmol) in DMF (0.4 mL) was stirred at 40° C. for 16 hours. Aqueous NaOH (166.7 μL, 3M) and methanol (0.2 mL) were added and the mixture was stirred at 40° C. for 1 hour. The reaction mixture was diluted with MeOH, filtered and purification by reverse phase HPLC using a gradient of ACN in Water (1-99%) and HCl as a modifier to give 5-(2-(4-fluorophenoxy)-4-(trifluoromethyl)benzamido)picolinic acid (56) (9.95 mg, 33%). ESI-MS m/z calc. 420.07. found 421.29 (M+1)+; Retention time: 1.60 minutes (3 minutes run). 1H NMR (400 MHz, DMSO) δ 13.15-12.96 (m, 1H), 11.09 (s, 1H), 8.90 (s, 1H), 8.28 (d, J=8.0 Hz, 1H), 8.07 (d, J=8.8 Hz, 1H), 7.92 (d, J=7.8 Hz, 1H), 7.66 (d, J=7.9 Hz, 1H), 7.36-7.13 (m, 5H) ppm.

Workup

  1. filtrationfiltered
  2. custompurification by reverse phase HPLC

Sources & evidence

ORD record
ord-95bcd3ff128545cfbbe56fe17e520852
Source dataset
uspto-grants-2016_08
Patent number
US09421196B2

Reaction notes

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