Sodium Carbonate → 3-[6-(1-Hydroxyethyl)pyridin-3-yl]-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}benzoic acid

HRID 2207433Notes

Reaction equation

HRID 2207433 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH:8]([OH:10])[CH3:9])=[N:6][CH:7]=1.OB(O)[C:13]1[CH:14]=[C:15]([CH:19]=[C:20]([NH:22][C:23]2[N:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[CH:25][N:24]=2)[CH:21]=1)[C:16]([OH:18])=[O:17].C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CN(C=O)C>[OH:10][CH:8]([C:5]1[N:6]=[CH:7][C:2]([C:13]2[CH:14]=[C:15]([CH:19]=[C:20]([NH:22][C:23]3[N:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[CH:25][N:24]=3)[CH:21]=2)[C:16]([OH:18])=[O:17])=[CH:3][CH:4]=1)[CH3:9]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 426142881-(5-Bromopyridin-2-yl)ethanolHCID 131735921HCID 131735921, compound

Product 1

HCID 1180925403-[6-(1-Hydroxyethyl)pyridin-3-yl]-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}benzoic acidYield 72.2%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 1-(5-bromopyridin-2-yl)ethanol (40.3 mg, 0.199 mmol), 3-(dihydroxyboranyl)-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}benzoic acid (31.8 mg, 0.072 mmol), PdCl2(dppf) (11.9 mg, 0.016 mmol), sodium carbonate (2 M, 0.15 mL, 0.300 mmol) and DMF (2 mL) was flushed and purged with Ar(g) (3×) and irradiated in a microwave reactor for 15 minutes at 120° C. The mixture was filtered and was directly purified by reverse phase HPLC to afford 3-[6-(1-hydroxyethyl)pyridin-3-yl]-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}benzoic acid (26.7 mg, 0.052 mmol, 71.4%). MS APCI C19H16F3N4O3 [M+H]+ 405. found 405. 1H NMR (500 MHz, DMSO-d6) δ13.1 (s, 1H), 10.54 (s, 1H), 8.88 (d, J=5.1 Hz, 1H), 8.77 (s, 1H), 8.38 (d, J=7.9 Hz, 2H), 8.15 (d, J=8.0 Hz, 1H), 7.86 (s, 1H), 7.68 (d, J=8.0 Hz, 1H), 7.34 (d, J=5.1 Hz, 1H), 4.82 (q, J=6.0 Hz, 1H), 1.41 (d, J=6.0 Hz, 3H).

Workup

  1. customwas flushed
  2. custompurged with Ar(g) (3×)
  3. customirradiated in a microwave reactor for 15 minutes at 120° C
  4. filtrationThe mixture was filtered
  5. customwas directly purified by reverse phase HPLC

Sources & evidence

ORD record
ord-01188921b6804fafba7e8b1a6d76f2da
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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