Binap, (A+-)- → 1-(2-(6-(hydroxymethyl)pyridin-3-ylamino)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethylpropan-1-one

HRID 716047Notes

Reaction equation

HRID 716047 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[CH:27]=[CH:28][C:29]([CH2:32][OH:33])=[N:30][CH:31]=1.CC([O-])(C)C.[Na+].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>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[OH:33][CH2:32][C:29]1[N:30]=[CH:31][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)=[CH:27][CH:28]=1

Participants

7

Reactant 4

HCID 634876Binap, (A+-)-HCID 20583240(5-Aminopyridin-2-YL)methanolHCID 23676156Sodium t-butoxideHCID 578292211-(2-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-yl)-2,2-dimethylpropane-1-one

Product 1

HCID 710153681-(2-(6-(hydroxymethyl)pyridin-3-ylamino)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethylpropan-1-oneYield 36.2%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 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 (0.25 g, 0.000606 mole) and (5-aminopyridin-2-yl)methanol (0.09 g, 0.00728 mole) was taken in toluene (3.0 ml). The reaction mixture was purged with argon for 15 min at RT and NaOtBu (0.11 g, 0.00121 mole) was added and the reaction mixture was further purged for 30 min with argon. BINAP (0.037 g, 0.000060 mole) and Pd2(dba)3 (0.027 g, 0.000030 mole) were added and the reaction mixture was heated to 110° C. for 3 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 with 40-50% ethyl acetate in hexanes to yield 0.1 g of 1-(2-(6-(hydroxymethyl)pyridin-3-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. customthe reaction mixture was further purged for 30 min with argon
  4. customAfter completion of the reaction
  5. filtrationthe reaction mixture was filtered through celite bed
  6. washwashed with ethyl acetate
  7. customFiltrate was collected
  8. concentrationconcentrated
  9. customto afford crude product which
  10. customwas purified
  11. customcolumn purification
  12. washby eluting with 40-50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-f68197c05a504519909fdcd813f7d587
Source dataset
uspto-grants-2015_11
Patent number
US09187487B2

Reaction notes

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