Sodium Bicarbonate → HCID 89783119, compound

HRID 58102Notes

Reaction equation

HRID 58102 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:31]([NH:33][CH:34]([CH3:36])[CH3:35])=[O:32])[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:31]([NH:33][CH:34]([CH3:36])[CH3:35])=[O:32])[N:26]=1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 195255172-(4-bromo-3,5-dimethyl-1H-pyrazol-1-yl)-N-isopropylacetamideHCID 897828064-(Tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-indazole

Product 2

HCID 6422Trifluoroacetic acidHCID 89783119HCID 89783119, compoundYield 28.8%

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 (58.3 mg, 0.187 mmol), 2-(4-bromo-3,5-dimethyl-1H-pyrazol-1-yl)-N-isopropylacetamide (77 mg, 0.28 mmol), PdCl2(dppf) (13.66 mg, 0.019 mmol), sodium bicarbonate (0.399 mL, 0.747 mmol), 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 (10.2 mg, 11.1%). 1H NMR (400 MHz, CD3OD) δ ppm 1.20 (d, J=6.57 Hz, 6H), 2.15 (s, 3H), 2.19 (s, 3H), 2.66 (s, 1H), 7.23 (s, 1H), 7.87 (s, 1H), 8.00 (d, J=1.01 Hz, 1H); ESI-MS m/z [M+H]+ calc'd for C18H20F3N5O, 380.2. found 380.3.

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-3785404d972946d687747eacccee6f7f
Source dataset
uspto-grants-2016_09
Patent number
US09434743B2

Reaction notes

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