Tetrahydrofuran → N-{2,4-Dimethyl-5-[6-(pyridin-3-yl)-1H-imidazo[1,2-b]pyrazol-1-yl]phenyl}-3-(3-methyloxetan-3-yl)benzamide

HRID 1055757Notes

Reaction equation

HRID 1055757 reaction equation
N12CCCN=C1CCCCC2.C[C:13]1[C:19]([N:20]2[C:27]3[N:23]([N:24]=[C:25]([C:28]4[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=4)[CH:26]=3)[CH:22]=[CH:21]2)=[C:18]([CH3:34])[CH:17]=[CH:16][C:14]=1[NH2:15].Br[C:36]1[CH:37]=[C:38]([C:42]2([CH3:46])[CH2:45][O:44][CH2:43]2)[CH:39]=[CH:40][CH:41]=1.F[B-](F)(F)F.[C:52]([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.C1C[O:68][CH2:67]C1>[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Mo].CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC(O)=O.CC(O)=O.[Pd].[Pd].O>[CH3:52][C:16]1[CH:17]=[C:18]([CH3:34])[C:19]([N:20]2[C:27]3[N:23]([N:24]=[C:25]([C:28]4[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=4)[CH:26]=3)[CH:22]=[CH:21]2)=[CH:13][C:14]=1[NH:15][C:67](=[O:68])[C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([C:42]2([CH3:46])[CH2:45][O:44][CH2:43]2)[CH:37]=1

Participants

9

Reactant 5

HCID 8028TetrahydrofuranHCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene2×HCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 687278353-(3-Bromophenyl)-3-methyloxetaneHCID 89699939HCID 89699939, compound

Product 1

HCID 89700017N-{2,4-Dimethyl-5-[6-(pyridin-3-yl)-1H-imidazo[1,2-b]pyrazol-1-yl]phenyl}-3-(3-methyloxetan-3-yl)benzamide

Reagents, catalysts & solvents 3

HCID 98885Molybdenum carbonyl (Mo(CO)6)CatalystHCID 11104995trans-Bis(acetato)bis[2-[bis(2-methylphenyl)phosphino]benzyl]dipalladium(II)CatalystHCID 962WaterSolvent

Conditions

Temperature
140 °C

Procedure

In a microwave reaction vessel, 302 mg (1.98 mmol) of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) were added to a mixture of 200 mg (0.660 mmol) of the compound of Example 11A, 150 mg (0.660 mmol) of the compound of Example 99A, 209 mg (0.793 mmol) of molybdenum hexacarbonyl, 19 mg (0.066 mmol) of tri-tert-butylphosphonium tetrafluoroborate and 62 mg (0.066 mmol) of trans-bis-(acetato)-bis-[o-(di-o-tolylphosphino)benzyl]dipalladium(II) in 4.5 ml of THF. After addition of the DBU, the reaction vessel was quickly closed with a crimp closure. The mixture was then heated in a microwave oven (Biotage Initiator, with Dynamic Field Tuning) at 140° C. for 30 min. After cooling to RT, about 15 ml of water were added and the reaction mixture was extracted three times with in each case about 15 ml of ethyl acetate. The combined organic extracts were washed with saturated aqueous sodium chloride solution and then dried over magnesium sulphate. After filtration and evaporation of the solvent, the residue that remained was separated into its components by preparative HPLC (Method 33). Since the product fractions were still impure, the preparative HPLC purification was repeated with this fraction using the same method. This gave an impure fraction of 15 mg and a clean fraction consisting of 6 mg (2% of theory) of the title compound.

Workup

  1. customthe reaction vessel was quickly closed with a crimp closure
  2. temperatureAfter cooling to RT
  3. extractionthe reaction mixture was extracted three times with in each case about 15 ml of ethyl acetate
  4. washThe combined organic extracts were washed with saturated aqueous sodium chloride solution
  5. dry with materialdried over magnesium sulphate
  6. filtrationAfter filtration and evaporation of the solvent
  7. customthe residue that remained was separated into its components by preparative HPLC (Method 33)
  8. customthe preparative HPLC purification
  9. customThis gave an impure fraction of 15 mg

Sources & evidence

ORD record
ord-4f82c1ccb24842ccae1ba98010bc3d1b
Source dataset
uspto-grants-2016_07
Patent number
US09394309B2

Reaction notes

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