Water → HCID 71281287, compound

HRID 475988

Reaction equation

HRID 475988 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.[CH3:27][NH:28][S:29]([C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1)(=[O:31])=[O:30].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>[CH3:24][C:23]1[CH:22]=[C:21]([CH3:25])[NH:20][C:19](=[O:26])[C:18]=1[CH2:17][NH:16][C:14]([C:4]1[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=[C:2]([C:35]2[CH:34]=[CH:33][C:32]([S:29]([NH:28][CH3:27])(=[O:30])=[O:31])=[CH:37][CH:36]=2)[CH:3]=1)=[O:15]

Participants

7

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 441187634-((Methylamino)sulphonyl)benzene boronic 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 71281287HCID 71281287, compoundYield 28.5%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
150 °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 (75 mg, 0.2 mmol), {4-[(methylamino)sulfonyl]phenyl}boronic acid (69 mg, 0.32 mmol) in DME/water (3 ml:1 ml). PdCl2(dppf)-CH2Cl2 adduct (8.2 mg, 0.01 mmol) was added and the resulting mixture was degassed with nitrogen for 10 min. Sodium bicarbonate (50.6 mg, 0.6 mmol) was added, the vessel was sealed, and the insoluble mixture was heated in a microwave at 150° C. for 30 min. After cooling, 2 mL of water was added to the mixture and solids that precipitated were filtered. DCM/MeOH (1:1) was added and the solution was filtered through a pad of silica gel and the filtrate was evaporated. The residue was purified by silica gel chromatography (eluent: gradient of 0 to 90:10 DCM/MeOH) and the isolated solid triturated in EtOAc. The solids were filtered and dried to afford the title compound (29 mg, 28%) as an off-white solid. LCMS E-S (M+H)=509.0. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.58 (br. s., 1H), 8.99 (t, J=4.93 Hz, 1H), 8.47 (m, J=8.59 Hz, 2H), 8.43 (s, 1H), 8.25 (s, 1H), 7.95 (m, J=8.59 Hz, 2H), 7.60 (br. s., 1H), 5.91 (s, 1H), 5.36 (quin, J=6.69 Hz, 1H), 4.42 (d, J=4.80 Hz, 2H), 2.46 (s, 3H), 2.23 (s, 3H), 2.13 (s, 3H), 1.56 (d, J=6.82 Hz, 6H).

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. additionDCM/MeOH (1:1) was added
  8. filtrationthe solution was filtered through a pad of silica gel
  9. customthe filtrate was evaporated
  10. customThe residue was purified by silica gel chromatography (eluent: gradient of 0 to 90:10 DCM/MeOH)
  11. customthe isolated solid triturated in EtOAc
  12. filtrationThe solids were filtered
  13. customdried

Sources & evidence

ORD record
ord-b51b4ad3e14f450391ac0c2265a95d25
Source dataset
uspto-grants-2014_01
Patent number
US08637509B2

Linked notes

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