Sodium Iodide → HCID 57484938, compound

HRID 1522368Notes

Reaction equation

HRID 1522368 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.[I-].[Na+].C(N(CC)CC)C.C1CCN2C(=NCCC2)CC1.[CH3:47][C:48]([OH:52])([C:50]#[CH:51])[CH3:49]>[Zn].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1COCC1.CCOC(C)=O.O.CS(C)=O>[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:51]#[C:50][C:48]([OH:52])([CH3:49])[CH3:47])[CH:3]=1)=[O:15]

Participants

11

Reactant 5

HCID 5238Sodium IodideHCID 82582-Methyl-3-butyn-2-olHCID 8471TriethylamineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 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 57484938HCID 57484938, compoundYield 67%

Reagents, catalysts & solvents 5

HCID 23994ZincCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 21939870Tetrahydrofuran ethyl acetateSolvent

Conditions

Temperature
90 °C

Procedure

To a 10 mL microwave vial were sequentially added 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 (0.15 g, 0.401 mmol), sodium iodide (0.012 g, 0.080 mmol), zinc (5.25 mg, 0.080 mmol), DMSO(2.5 mL), triethylamine (0.112 mL, 0.802 mmol), and DBU (0.121 mL, 0.802 mmol). The suspension was stirred and degassed with nitrogen for 5 min, forming an emulsion. Next added 2-methyl-3-butyn-2-ol (0.194 mL, 2.006 mmol) and Pd(Ph3P)4 (0.046 g, 0.040 mmol). The stirring contents were heated at 90° C. for 3 hr, and then allowed to cool to room temperature. The reaction mixture was poured into a solution of water and 20% THF/EtOAc, and stirred. The layers were separated, and the organic layer washed with brine. The organic layer was dried over MgSO4, and then filtered through Celite, washing the filter pad with additional EtOAc. The filtrate was concentrated in vacuo and the crude residue dried overnight on a hi-vac pump. The crude product was purified by silica gel chromatography (eluent: gradient: 5-80% of DCM and Chloroform containing 10% 2M Ammonia (in methanol)). The collected product was dried in vacuum oven at 45° C. overnight, to afford the final product as 0.116 g (67% yield). LCMS E-S (M+H)=421.9. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.44-1.55 (m, 12 H), 2.13 (s, 3 H), 2.20 (s, 3 H), 4.35 (d, J=4.80 Hz, 2 H), 5.15-5.26 (m, 1 H), 5.70 (s, 1 H), 5.89 (s, 1 H), 7.65 (s, 1 H), 8.38 (s, 1 H), 8.93 (t, J=4.80 Hz, 1 H), 11.55 (s, 1 H).

Workup

  1. customdegassed with nitrogen for 5 min
  2. customforming an emulsion
  3. temperatureto cool to room temperature
  4. stirringstirred
  5. customThe layers were separated
  6. washthe organic layer washed with brine
  7. dry with materialThe organic layer was dried over MgSO4
  8. filtrationfiltered through Celite
  9. washwashing the filter pad with additional EtOAc
  10. concentrationThe filtrate was concentrated in vacuo
  11. dry with materialthe crude residue dried overnight on a hi-vac pump
  12. customThe crude product was purified by silica gel chromatography (eluent: gradient: 5-80% of DCM and Chloroform containing 10% 2M Ammonia (in methanol))
  13. customThe collected product was dried in vacuum oven at 45° C. overnight

Sources & evidence

ORD record
ord-9f0e76234e924716ba4593608049a714
Source dataset
uspto-grants-2015_07
Patent number
US09073924B2

Reaction notes

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