Sodium Bicarbonate → Trifluoroacetic acid

HRID 58103Notes

Reaction equation

HRID 58103 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[C:14]3[C:10]=2[CH:11]=[N:12][NH:13]3)O1.Br[C:24]1[C:25]([CH3:37])=[N:26][N:27]([CH2:30][C@H:31]2[NH:35][C:34](=[O:36])[CH2:33][CH2:32]2)[C:28]=1[CH3:29].[C:38](=[O:41])(O)[O-:39].[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].O1CCOCC1>[C:38]([OH:39])([C:18]([F:21])([F:20])[F:19])=[O:41].[CH3:37][C:25]1[C:24]([C:9]2[CH:17]=[C:16]([C:18]([F:19])([F:20])[F:21])[CH:15]=[C:14]3[C:10]=2[CH:11]=[N:12][NH:13]3)=[C:28]([CH3:29])[N:27]([CH2:30][C@H:31]2[NH:35][C:34](=[O:36])[CH2:33][CH2:32]2)[N:26]=1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 897828064-(Tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-indazoleHCID 89794698HCID 89794698, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 89794819(5S)-5-((3,5-dimethyl-4-(6-(trifluoromethyl)-1H-indazol-4-yl)-1H-pyrazol-1-yl)methyl)pyrrolidin-2-one

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-indazole, (S)-5-((4-bromo-3,5-dimethyl-1H-pyrazol-1-yl)methyl)pyrrolidin-2-one, PdCl2(dppf), sodium bicarbonate, and dioxane (2 mL) were mixed in a 10 mL vial to give an orange suspension. The vial was sealed and then heated to 140° C. for 45 minutes in a microwave reactor. The reaction mixture was subsequently filtered and the product was purified by preparative HPLC, eluting with a gradient of 35-55% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA). The pure fractions were lyophilized to give a TFA salt of the title compound as a white solid (8 mg). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.98 (s, 3H), 2.10 (s, 3H), 2.16 (s, 3H), 4.09 (d, J=5.31 Hz, 2H), 7.16 (s, 1H), 7.81 (s, 1H), 7.86 (s, 1H), 8.03 (s, 1H); ESI-MS m/z [M+H]+ calc'd for C18H18F3N5O, 378.1. found 378.3.

Workup

  1. customto give an orange suspension
  2. customThe vial was sealed
  3. filtrationThe reaction mixture was subsequently filtered
  4. customthe product was purified by preparative HPLC
  5. washeluting with a gradient of 35-55% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA)

Sources & evidence

ORD record
ord-2b561ada1cde49369c1b0eb352517b53
Source dataset
uspto-grants-2016_09
Patent number
US09434743B2

Reaction notes

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