Sodium Carbonate → 6-(3-{2-tert-Butyl-6-oxo-4H,5H,6H-thieno[2,3-c]pyrrol-5-yl}-2-methylphenyl)-4-({5-methyl-4H,5H,6H,7H-pyrazolo[1,5-a]pyrazin-2-yl}amino)-2,3-dihydropyridazin-3-one

HRID 872144Notes

Reaction equation

HRID 872144 reaction equation
Cl[C:2]1[CH:3]=[C:4]([NH:9][C:10]2[CH:19]=[C:13]3[CH2:14][N:15]([CH3:18])[CH2:16][CH2:17][N:12]3[N:11]=2)[C:5](=[O:8])[NH:6][N:7]=1.[C:20]([C:24]1[S:31][C:30]2[C:29](=[O:32])[N:28]([C:33]3[CH:38]=[CH:37][CH:36]=[C:35](B4OC(C)(C)C(C)(C)O4)[C:34]=3[CH3:48])[CH2:27][C:26]=2[CH:25]=1)([CH3:23])([CH3:22])[CH3:21].O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+]>C(OCC)(=O)C.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>[C:20]([C:24]1[S:31][C:30]2[C:29](=[O:32])[N:28]([C:33]3[C:34]([CH3:48])=[C:35]([C:2]4[CH:3]=[C:4]([NH:9][C:10]5[CH:19]=[C:13]6[CH2:14][N:15]([CH3:18])[CH2:16][CH2:17][N:12]6[N:11]=5)[C:5](=[O:8])[NH:6][N:7]=4)[CH:36]=[CH:37][CH:38]=3)[CH2:27][C:26]=2[CH:25]=1)([CH3:23])([CH3:21])[CH3:22]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 585403166-chloro-4-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)pyridazin-3(2H)-oneHCID 898241832-tert-Butyl-5-(2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4H-thieno[3,2-c]pyrrol-6(5H)-one

Product 1

HCID 569290576-(3-{2-tert-Butyl-6-oxo-4H,5H,6H-thieno[2,3-c]pyrrol-5-yl}-2-methylphenyl)-4-({5-methyl-4H,5H,6H,7H-pyrazolo[1,5-a]pyrazin-2-yl}amino)-2,3-dihydropyridazin-3-one

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Procedure

In a dried pressure flask was placed 0.968 mmol of 101m, 1.065 mmol of 101g, and 56 mg (5 mol %) of tetrakis(triphenylphosphine)palladium(0), The flask was evacuated under vacuum, then filled with nitrogen. This procedure was repeated twice more, then 8 mL of anhydrous dioxane and 2.4 mL (2.5 equivalents) of 1 M aqueous sodium carbonate solution were added, and the mixture was heated at 100° for 18 h. The mixture was cooled to room temperature, then diluted with ethyl acetate, washed with saturated aqueous saturated NaCl solution four times, dried over anhydrous Na2SO4, and purified by chromatography on a Biotage 25M KP NH column to afford 101. 1H NMR (400 MHz, DMSO) δ 12.96 (s, 1H), 9.19 (s, 1H), 7.78 (s, 1H), 7.54-7.32 (m, 3H), 7.15 (s, 1H), 5.97 (s, 1H), 4.78 (s, 2H), 3.97 (t, J=5.3, 2H), 3.52 (s, 2H), 2.80 (t, J=5.4, 2H), 2.36 (s, 3H), 2.11 (d, J=12.1, 3H), 1.42 (s, 9H). ESIMS m/z=530.2 (M+1).

Workup

  1. customIn a dried pressure flask was placed
  2. additionfilled with nitrogen
  3. temperaturethe mixture was heated at 100° for 18 h
  4. washwashed with saturated aqueous saturated NaCl solution four times
  5. dry with materialdried over anhydrous Na2SO4
  6. custompurified by chromatography on a Biotage 25M KP NH column

Sources & evidence

ORD record
ord-b1e6ed06ec934978bfc3d6affc003907
Source dataset
uspto-grants-2015_03
Patent number
US08975260B2

Reaction notes

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