Sodium Bicarbonate → HCID 56598005, compound

HRID 1522381Notes

Reaction equation

HRID 1522381 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.[NH2:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1.C(=O)(O)[O-].[Na+].C(Cl)Cl.CO>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>[NH2:27][C:28]1[CH:33]=[CH:32][C:31]([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:30][CH:29]=1

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 27346154-Aminophenylboronic acidHCID 21226129Dichloromethane methanolHCID 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 56598005HCID 56598005, compoundYield 69.7%

Reagents, catalysts & solvents 2

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

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-aminophenyl)boronic acid (44 mg, 0.32 mmol) in DME/water (3 ml:1 ml). PdCl2(dppf)-CH2Cl2 adduct (8.74 mg, 0.011 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 pink mixture was irradiated (microwave) at 150° C. for 30 min. After cooling, DCM/MeOH (1:1) was added, it was pre-absorbed on silica gel and purified by silica gel chromatography (eluent: gradient 0 to 90:10:1 DCM/MeOH/NH4OH). The isolated solid was treated with MeOH. The solids that precipitated were filtered and dried to afford the title compound (63 mg, 66%) as a yellow solid. LCMS E-S (M+H)=431.3. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.56 (s, 1 H), 8.88 (t, J=4.93 Hz, 1 H), 8.27 (s, 1 H), 8.01 (s, 1 H), 7.99 (d, J=2.02 Hz, 2 H), 6.69 (s, 1 H), 6.67 (s, 1 H), 5.90 (s, 1 H), 5.61 (s, 2 H), 5.24-5.32 (m, 1 H), 4.40 (d, J=4.80 Hz, 2 H), 2.22 (s, 3 H), 2.13 (s, 3 H), 1.53 (s, 3 H), 1.51 (s, 3 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. customthe insoluble light pink mixture was irradiated (microwave) at 150° C. for 30 min
  5. temperatureAfter cooling
  6. customit was pre-absorbed on silica gel
  7. custompurified by silica gel chromatography (eluent: gradient 0 to 90:10:1 DCM/MeOH/NH4OH)
  8. additionThe isolated solid was treated with MeOH
  9. customThe solids that precipitated
  10. filtrationwere filtered
  11. customdried

Sources & evidence

ORD record
ord-a458edd8a9434333894b730fba877a9e
Source dataset
uspto-grants-2015_07
Patent number
US09073924B2

Reaction notes

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