Sodium Carbonate → HCID 24889465, compound

HRID 1783931Notes

Reaction equation

HRID 1783931 reaction equation
CN1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([NH:14][C:15]3[C:16]4[N:17]([N:29]=[CH:30][N:31]=4)[C:18](C4C=C(C(N)=O)SC=4)=[CH:19][N:20]=3)=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.N1(C2C=CC(N)=CC=2)CC[O:35]CC1.[NH:45]1[CH:49]=[CH:48][CH2:47][N:46]1B(O)O.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C([O-])(O)=O.[Na+].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>[N:5]1([C:8]2[CH:9]=[CH:10][C:11]([NH:14][C:15]3[C:16]4[N:17]([N:29]=[CH:30][N:31]=4)[C:18]([C:49]4[NH:45][N:46]=[CH:47][CH:48]=4)=[CH:19][N:20]=3)=[CH:12][CH:13]=2)[CH2:6][CH2:7][O:35][CH2:3][CH2:4]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 75655Benzenamine, 4-(4-morpholinyl)-HCID 575899284-{8-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl}-thiophene-2-carboxylic acid amideHCID 67047414HCID 67047414, compound

Product 1

HCID 24889465HCID 24889465, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
100 °C

Procedure

This compound may be prepared using methods as described for Compound 6, step 4, using 5-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-[4-(morpholin-4-yl)-phenyl]-amine (100 mg, 0.267 mmol), 1H-pyrazole-2-boronic acid (60 mg, 0.535 mmol), Pd(PPh3)4 (93 mg, 0.08 mmol) and Na2CO3 (88 mg, 0.80 mmol) in DMF (2 mL). The reaction mixture is placed in a stem-tube and stirred at 100° C. for 18 hours. After cooling, the mixture is diluted with NaHCO3 solution and extracted with EtOAc (4×). The organic layer is washed with water, dried over MgSO4, filtered and evaporated to afford a crude product that is purified by silica gel column chromatography eluting with DCM followed by 96:4 DCM:NH3 (7M in MeOH). The title compound is isolated after trituration with diethyl ether (12.4 mg, 13%). Conversion into the mesylate salt using 0.1M methanesulfonic acid (0.342 mL, 0.0342 mmol) gives the target compound (10 mg, 81%). 1H-NMR (400 MHz, d6-DMSO) δ(ppm) 2.34 (3H, s, MsOH), 3.14 (4H, m), 3.81 (4H, m), 7.04 (2H, d), 7.27 (1H, m), 7.92 (3H, m), 8.24 (1H, s), 8.76 (1H, s), 9.92 (1H, s). LCMS: Rt 2.45 min (97.6%), m/z (APCI) 363 (M+H)+.

Workup

  1. customThis compound may be prepared
  2. customThe reaction mixture is placed in a stem-tube
  3. temperatureAfter cooling
  4. extractionextracted with EtOAc (4×)
  5. washThe organic layer is washed with water
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customto afford a crude product that
  10. customis purified by silica gel column chromatography
  11. washeluting with DCM

Sources & evidence

ORD record
ord-033ea64afce44276a7c4dac91d4384c8
Source dataset
uspto-grants-2009_03
Patent number
US07501411B2

Reaction notes

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