Cesium carbonate → HCID 71015501, compound

HRID 716042Notes

Reaction equation

HRID 716042 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:10]([C:11](=[O:16])[C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:9][N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:5]2=[N:6][CH:7]=1.[NH2:25][C:26]1[N:31]=[CH:30][C:29]([CH2:32][OH:33])=[CH:28][CH:27]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[OH:33][CH2:32][C:29]1[CH:28]=[CH:27][C:26]([NH:25][C:2]2[N:3]=[C:4]3[C:10]([C:11](=[O:16])[C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:9][N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:5]3=[N:6][CH:7]=2)=[N:31][CH:30]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 2794829(6-Aminopyridin-3-yl)methanolHCID 578292211-(2-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-yl)-2,2-dimethylpropane-1-one

Product 1

HCID 71015501HCID 71015501, compoundYield 45.3%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a 35 ml seal tube, 1-(2-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-yl)-2,2-dimethylpropane-1-one (1.0 g, 0.00242 mole) and (6-aminopyridin-3-yl)methanol (0.36 g, 0.00291 mole) was taken in toluene (10.0 ml). The reaction mixture was purged with argon for 15 min at RT followed by Cs2CO3 (3.1 g, 0.0097 mole) was added and further purged for 30 min with argon. BINAP (0.03 g, 0.000048 mole) and Pd(OAc)2 (0.01 g, 0.000048 mole) were added and the reaction mixture was heated to 110° C. for 16 hrs. After completion of the reaction, the reaction mixture was filtered through celite bed and washed with ethyl acetate. Filtrate was collected and concentrated to afford crude product which was purified using column purification by eluting the compound with 20-25% ethyl acetate in hexanes to yield 0.5 g of 1-(2-(5-(hydroxymethyl)pyridin-2-ylamino)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethylpropan-1-one.

Workup

  1. customTo a 35 ml seal tube
  2. customThe reaction mixture was purged with argon for 15 min at RT
  3. additionwas added
  4. customfurther purged for 30 min with argon
  5. customAfter completion of the reaction
  6. filtrationthe reaction mixture was filtered through celite bed
  7. washwashed with ethyl acetate
  8. customFiltrate was collected
  9. concentrationconcentrated
  10. customto afford crude product which
  11. customwas purified
  12. customcolumn purification
  13. washby eluting the compound with 20-25% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-f27ab9846c1a426e98a233075ab22e35
Source dataset
uspto-grants-2015_11
Patent number
US09187487B2

Reaction notes

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