Dimethyl Sulfoxide → HCID 118208689, compound

HRID 595296Notes

Reaction equation

HRID 595296 reaction equation
Br[C:2]1[N:7]=[C:6]([NH:8][C:9]2N=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=2)[CH:5]=[CH:4][CH:3]=1.[NH:19]1[CH:23]=[C:22]([CH2:24][CH2:25][C:26]([O:28]CC)=[O:27])[CH:21]=[N:20]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:39]S(C)=O>>[F:18][C:15]([F:16])([F:17])[C:13]1[CH:12]=[CH:11][N:10]=[C:9]([NH:8][C:6]2[N:7]=[C:2]([N:20]3[CH:21]=[C:22]([CH2:24][CH2:25][C:26]([OH:28])=[O:27])[CH:23]=[N:19]3)[CH:3]=[CH:4][CH:5]=2)[CH:39]=1

Participants

5

Reactant 4

HCID 679Dimethyl Sulfoxide2×HCID 62657Potassium Phosphate, TribasicHCID 69025812HCID 69025812, compoundHCID 131734586HCID 131734586, compound

Product 1

HCID 118208689HCID 118208689, compound

Conditions

Temperature
130 °C

Procedure

N-(6-Bromopyridin-2-yl)-4-(trifluoromethyl)pyrimidin-2-amine (0.015 g, 0.047 mmol), ethyl 3-(1H-pyrazol-4-yl)propanoate (0.008 g, 0.047 mmol), potassium phosphate tribasic (0.030 g, 0.14 mmol), and DMSO (0.48 mL) were added to a microwave vial. The reaction tube was sealed and heated to 130° C. for 12 hours. The completed reaction was diluted DMSO (0.5 mL) and passed through a syringe filtered where the eluent was collected and concentrated under reduced pressure. The residue was taken up in dichloromethane (1.0 mL), MeOH (0.5 mL), and NaOH (0.5 mL, 1.0 M) and was allowed to stir at ambient temperature for 4 hours. The reaction was concentrated under reduced pressure. The residue was taken up in DMSO (1.0 mL), passed through a syringe filter and purified by reverse phase preparative HPLC (0 to 95% ACN/H2O with 0.1% ammonium hydroxide modifier) to afford 3-(1-(6-((4-(trifluoromethyl)pyridin-2-yl)amino)pyridin-2-yl)-1H-pyrazol-4-yl)propanoic acid. MS ESI calc. for C12H15F3N5O2 [M+H]+ 378. found 378. 1H NMR (600 MHz, DMSO-d6) δ 10.35 (s, 1H), 8.48 (d, J=5.2, 1H), 8.19 (s, 1H), 8.18 (s, 1H), 7.80 (t, J=8.0, 1H), 7.60 (s, 1H), 7.49 (d, J=8.2, 1H), 7.34 (d, J=7.8, 1H), 7.20 (d, J=5.3, 1H), 2.62 (t, J=7.6, 2H), 2.23 (t, 2H).

Workup

  1. customThe reaction tube was sealed
  2. customThe completed reaction
  3. custompassed through a syringe
  4. filtrationfiltered where the eluent
  5. customwas collected
  6. concentrationconcentrated under reduced pressure
  7. concentrationThe reaction was concentrated under reduced pressure
  8. custompassed through a syringe
  9. filtrationfilter
  10. custompurified by reverse phase preparative HPLC (0 to 95% ACN/H2O with 0.1% ammonium hydroxide modifier)

Sources & evidence

ORD record
ord-d96f8a132414450e99f3b3c534ac4ff5
Source dataset
uspto-grants-2016_01
Patent number
US09242984B2

Reaction notes

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