Hydrochloric Acid → N-{2-[1-(2-fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazol-3-yl]-5-methoxy-6-(pyridin-4-ylamino)pyrimidin-4-yl}-2-methoxyacetamide

HRID 1482931Notes

Reaction equation

HRID 1482931 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[C:9]3[CH2:23][CH2:22][CH2:21][C:10]=3[N:11]([CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[F:20])[N:12]=2)[N:5]=[C:4]([NH:24][C:25](=[O:29])[CH2:26][O:27][CH3:28])[C:3]=1[O:30][CH3:31].Cl.Br[C:34]1[CH:39]=[CH:38][N:37]=[CH:36][CH:35]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl>CN(C=O)C.O.C([O-])(=O)C.C([O-])(=O)C.[Pd+2]>[F:20][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[CH2:13][N:11]1[C:10]2[CH2:21][CH2:22][CH2:23][C:9]=2[C:8]([C:6]2[N:5]=[C:4]([NH:24][C:25](=[O:29])[CH2:26][O:27][CH3:28])[C:3]([O:30][CH3:31])=[C:2]([NH:1][C:34]3[CH:39]=[CH:38][N:37]=[CH:36][CH:35]=3)[N:7]=2)=[N:12]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 881004-Bromopyridinium chlorideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 90015879N-{6-amino-2-[1-(2-fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]-pyrazol-3-yl]-5-methoxypyrimidin-4-yl}-2-methoxyacetamide

Product 1

HCID 72202406N-{2-[1-(2-fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazol-3-yl]-5-methoxy-6-(pyridin-4-ylamino)pyrimidin-4-yl}-2-methoxyacetamide

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
105 °C

Procedure

50 mg of N-{6-amino-2-[1-(2-fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]-pyrazol-3-yl]-5-methoxypyrimidin-4-yl}-2-methoxyacetamide 1-7-1 (0.12 mmol, 1.00 eq.), 25 mg of 4-bromopyridine hydrochloride (1:1) (0.13 mmol, 1.10 eq.), mg of (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.02 mmol, 0.15 eq.), 115 mg of caesium carbonate (0.36 mmol, 3.00 eq.) and 2.6 mg of palladium diacetate (0.012 mmol, 0.1 eq.) were suspended in 0.5 mL of dry DMF and stirred under nitrogen atmosphere at 105° C. bath temperature for two h. The reaction mixture was diluted with water, the pH was adjusted to 7.5 using 4N aqueous hydrochloric acid and the crude product was extracted with DCM. The combined organic layers were dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography yielding 29 mg (0.06 mmol, 49%) of analytically pure target compound.

Workup

  1. extractionthe crude product was extracted with DCM
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by flash chromatography
  5. customyielding 29 mg (0.06 mmol, 49%) of analytically pure target compound

Sources & evidence

ORD record
ord-21409567c7e1445694d895a847b23b7a
Source dataset
uspto-grants-2016_08
Patent number
US09416125B2

Reaction notes

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