Sodium Bicarbonate → HCID 89782936, compound

HRID 58105Notes

Reaction equation

HRID 58105 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[CH:25]=[CH:26][C:27]([S:30]([NH:33][CH2:34][CH2:35][OH:36])(=[O:32])=[O:31])=[N:28][CH:29]=1.[C:37](=[O:40])(O)[O-:38].[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:37]([OH:38])([C:18]([F:21])([F:20])[F:19])=[O:40].[OH:36][CH2:35][CH2:34][NH:33][S:30]([C:27]1[CH:26]=[CH:25][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)=[CH:29][N:28]=1)(=[O:32])=[O:31]

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 59406275HCID 59406275, compoundHCID 897828064-(Tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-indazole

Product 2

HCID 6422Trifluoroacetic acidHCID 89782936HCID 89782936, compoundYield 66.3%

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 (40 mg, 0.128 mmol), 5-bromo-N-(2-hydroxyethyl)pyridine-2-sulfonamide (43.2 mg, 0.154 mmol), PdCl2(dppf) (9.38 mg, 0.013 mmol), sodium bicarbonate (0.274 mL, 0.513 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 20 minutes in a microwave reactor. The reaction mixture was subsequently filtered and the product was purified by preparative HPLC, eluting with a gradient of 25-50% 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 (16.4 mg, 25.6%). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.05 (q, J=6.48 Hz, 2H), 3.40-3.46 (m, 7H), 7.70 (d, J=1.01 Hz, 1H), 7.96 (t, J=5.81 Hz, 1H), 8.08 (dd, J=8.21, 0.88 Hz, 2H), 8.45 (s, 1H), 8.51 (dd, J=8.21, 2.40 Hz, 1H), 9.15 (dd, J=2.27, 1.01 Hz, 1H); ESI-MS m/z [M+H]+ calc'd for C15H13F3N4O3S, 387.1. found 387.2.

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 25-50% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA)

Sources & evidence

ORD record
ord-0ddaf83dd57d4548ad7eaed76e6c9aae
Source dataset
uspto-grants-2016_09
Patent number
US09434743B2

Reaction notes

Loading…