Water → HCID 56598142, compound

HRID 1522382Notes

Reaction equation

HRID 1522382 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]2[C:19](=[O:26])[NH:20][C:21]([CH3:25])=[CH:22][C:23]=2[CH3:24])=[O:15])[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=1.[C:27]([NH:30][C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1)(=[O:29])[CH3:28].C(=O)(O)[O-].[Na+].O>COCCOC.O.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].C(Cl)Cl>[C:27]([NH:30][C:31]1[CH:36]=[CH:35][C:34]([C:2]2[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]3[C:19](=[O:26])[NH:20][C:21]([CH3:25])=[CH:22][C:23]=3[CH3:24])=[O:15])[C:5]3[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=3[N:7]=2)=[CH:33][CH:32]=1)(=[O:29])[CH3:28]

Participants

7

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 27346574-Acetamidophenylboronic acidHCID 565974256-Chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

Product 1

HCID 56598142HCID 56598142, compoundYield 55.4%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
110 °C

Procedure

In a 25 mL sealable tube under nitrogen were combined 6-chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (80 mg, 0.21 mmol) and [4-(acetylamino)phenyl]boronic acid (57.5 mg, 0.32 mmol) in DME/water (3 ml:1 ml). PdCl2(dppf)-CH2Cl2 adduct (8.7 mg, 0.010 mmol) was added and the resulting mixture was degassed with nitrogen for 10 min. Sodium bicarbonate (53.9 mg, 0.64 mmol) was added, the vessel was sealed, and the insoluble light brown mixture was heated at 110° C. for 2.5 h. After cooling, 2 mL of water was added to the dark grey mixture and solids that precipitated were filtered. EtOAc was added, the mixture was heated and some hexanes were added. The solids were filtered, dissolved in DCM/MeOH (1:1) and 1 mL of DMF. The contents were pre-absorbed onto silica gel and purified by silica gel chromatography (eluent: gradient 0 to 90:10:1 DCM/MeOH/NH4OH). The isolated product was treated with MeOH, and the solids that precipitated were filtered, washed with hexanes and dried to afford the title compound (55 mg, 52%) as a white solid. LCMS E-S (M+H)=473.1. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.57 (s, 1 H), 10.18 (s, 1 H), 8.93 (t, J=4.93 Hz, 1 H), 8.35 (s, 1 H), 8.22 (m, J=8.84 Hz, 2 H), 8.13 (s, 1 H), 7.76 (m, J=8.84 Hz, 2 H), 5.91 (s, 1 H), 5.28-5.37 (m, 1 H), 4.41 (d, J=4.80 Hz, 2 H), 2.23 (s, 3 H), 2.13 (s, 3 H), 2.09 (s, 3 H), 1.54 (d, J=6.82 Hz, 6 H).

Workup

  1. customIn a 25 mL sealable tube under nitrogen were combined
  2. customthe resulting mixture was degassed with nitrogen for 10 min
  3. customthe vessel was sealed
  4. temperatureAfter cooling
  5. customthat precipitated
  6. filtrationwere filtered
  7. additionEtOAc was added
  8. temperaturethe mixture was heated
  9. additionsome hexanes were added
  10. filtrationThe solids were filtered
  11. dissolutiondissolved in DCM/MeOH (1:1)
  12. customThe contents were pre-absorbed onto silica gel
  13. custompurified by silica gel chromatography (eluent: gradient 0 to 90:10:1 DCM/MeOH/NH4OH)
  14. additionThe isolated product was treated with MeOH
  15. customthe solids that precipitated
  16. filtrationwere filtered
  17. washwashed with hexanes
  18. customdried

Sources & evidence

ORD record
ord-c2435cdeb80745ef963c8b8d5d57889c
Source dataset
uspto-grants-2015_07
Patent number
US09073924B2

Reaction notes

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