Triethylamine → HCID 178480686, compound

HRID 1487408Notes

Reaction equation

HRID 1487408 reaction equation
C(N(CC)CC)C.[F:8][C:9]1[CH:10]=[C:11]([S:16][C:17]2[N:18]=[C:19]3[C:25]([NH:26][C:27](=[O:54])[C:28]4[CH:33]=[CH:32][C:31]([N:34]5[CH2:39][CH2:38][N:37]([CH3:40])[CH2:36][CH2:35]5)=[CH:30][C:29]=4[N:41]([CH:48]4[CH2:53][CH2:52][O:51][CH2:50][CH2:49]4)C(=O)C(F)(F)F)=[N:24][N:23](C(=O)C4C=CC(N5CCN(C)CC5)=CC=4N(C4CCOCC4)C(=O)C(F)(F)F)[C:20]3=[N:21][CH:22]=2)[CH:12]=[C:13]([F:15])[CH:14]=1>CO>[F:8][C:9]1[CH:10]=[C:11]([S:16][C:17]2[N:18]=[C:19]3[C:25]([NH:26][C:27](=[O:54])[C:28]4[CH:33]=[CH:32][C:31]([N:34]5[CH2:35][CH2:36][N:37]([CH3:40])[CH2:38][CH2:39]5)=[CH:30][C:29]=4[NH:41][CH:48]4[CH2:49][CH2:50][O:51][CH2:52][CH2:53]4)=[N:24][NH:23][C:20]3=[N:21][CH:22]=2)[CH:12]=[C:13]([F:15])[CH:14]=1

Participants

4

Reactant 2

HCID 8471TriethylamineHCID 86680570HCID 86680570, compound

Product 1

HCID 178480686HCID 178480686, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
65 °C

Procedure

0.27 ml (1.95 mmol) of triethylamine is added to 0.21 g (0.19 mmol) of a solution of N-(5-(3,5-difluorophenylthio)-1-(4-(4-methylpiperazine-1-yl)-2-(2,2,2-trifluoro-N-(tetrahydro-2H-pyran-4-yl)acetamido)benzoyl)-1H-pyrazolo[3,4-b]pyrazine-3-yl)-4-(4-methylpiperazine-1-yl)-2-(2,2,2-trifluoro-N-(tetrahydro-2H-pyran-4-yl)acetamido)benzamide in 5 ml of methanol. The reaction medium is heated at 65° C. for 4 hours, and then overnight at room temperature. After evaporation of the solvent, the product is extracted several times with ethyl acetate. The organic phases are combined, washed with saturated sodium bicarbonate solution, dried on magnesium sulfate and concentrated. The residue is purified by silica gel chromatography (95:4:1 dichloromethane/methanol/ammonium as eluent) to yield 0.065 g (57%) of N-(5-(3,5-difluorophenylthio)-1-H-pyrazolo[3,4-b]pyrazine-3-yl)-4-(4-methylpiperazine-1-yl)-2-(tetrahydro-2H-pyran-4-ylamino)benzamide in the form of a yellow solid.

Workup

  1. customovernight
  2. customat room temperature
  3. customAfter evaporation of the solvent
  4. extractionthe product is extracted several times with ethyl acetate
  5. washwashed with saturated sodium bicarbonate solution
  6. customdried on magnesium sulfate
  7. concentrationconcentrated
  8. customThe residue is purified by silica gel chromatography (95:4:1 dichloromethane/methanol/ammonium as eluent)

Sources & evidence

ORD record
ord-95dd31655a2c4ad2819d97164940ef33
Source dataset
uspto-grants-2016_08
Patent number
US09428510B2

Reaction notes

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