Heptane → 3-[2-[Tert-butyl(dimethyl)silyl]oxyethyl]-2-[2-(4-isopropylsulfonylphenyl)-5-trityl-pyrrolo[2,3-b]pyrazin-7-yl]isoindolin-1-one

HRID 627801Notes

Reaction equation

HRID 627801 reaction equation
[CH:1]([S:4]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[C:15]3[C:21]([NH2:22])=[CH:20][N:19]([C:23]([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)[C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[C:16]3=[N:17][CH:18]=2)=[CH:9][CH:8]=1)(=[O:6])=[O:5])([CH3:3])[CH3:2].C[Al](C)C.CCCCCCC.[Si:53]([O:60][CH2:61][CH2:62][CH:63]1[C:71]2[C:66](=[CH:67][CH:68]=[CH:69][CH:70]=2)[C:65](=O)[O:64]1)([C:56]([CH3:59])([CH3:58])[CH3:57])([CH3:55])[CH3:54].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1(C)C=CC=CC=1.C(Cl)Cl.O>[Si:53]([O:60][CH2:61][CH2:62][CH:63]1[C:71]2[C:66](=[CH:67][CH:68]=[CH:69][CH:70]=2)[C:65](=[O:64])[N:22]1[C:21]1[C:15]2[C:16](=[N:17][CH:18]=[C:13]([C:10]3[CH:9]=[CH:8][C:7]([S:4]([CH:1]([CH3:3])[CH3:2])(=[O:6])=[O:5])=[CH:12][CH:11]=3)[N:14]=2)[N:19]([C:23]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)([C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:20]=1)([C:56]([CH3:59])([CH3:58])[CH3:57])([CH3:55])[CH3:54]

Participants

10

Reactant 6

HCID 8900HeptaneHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 16682925TrimethylaluminumHCID 711435912-(4-Isopropylsulfonylphenyl)-5-trityl-pyrrolo[2,3-b]pyrazin-7-amineHCID 711436383-(2-((tert-butyldimethylsilyl)oxy)ethyl)isobenzofuran-1(3H)-one

Product 1

HCID 711436503-[2-[Tert-butyl(dimethyl)silyl]oxyethyl]-2-[2-(4-isopropylsulfonylphenyl)-5-trityl-pyrrolo[2,3-b]pyrazin-7-yl]isoindolin-1-oneYield 66%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×

Procedure

2-(4-isopropylsulfonylphenyl)-5-trityl-pyrrolo[2,3-b]pyrazin-7-amine (125 mg, 0.2237 mmol) dissolved in PhMe (3 mL) under N2. AlMe3 in heptane (671.1 μL of 1.0 M, 0.6711 mmol) added at RT and the mixture stirred for 30 mins. A solution of 3-[2-[tert-butyl(dimethyl)silyl]oxyethyl]-3H-isobenzofuran-1-one (130.8 mg, 0.4474 mmol) in DCM (3 mL) added with cooling on an ice bath and the mixture stirred overnight. Reaction mixture re-cooled and water added slowly followed by DCM. After stirring for 30 mins, mixture passed through a phase separator cartridge and filtrate concentrated. Residue taken up in THF (5 mL) and PPh3 (88.02 mg, 0.3356 mmol) then DEAD (42.26 μL, 0.2684 mmol) added at RT under N2. Reaction mixture stirred overnight, then concentrated without heating. Residue partitioned between DCM and brine. Aqueous phase extracted with DCM and combined organics dried and concentrated. Residue taken up in DCM and purified by chromatography (silica, 0-100% EtOAc-petrol gradient elution) to give the title compound as a yellow foam (123 mg, 66% over 2 steps); MS (ES+) 833.3.

Workup

  1. temperaturewith cooling on an ice bath
  2. stirringthe mixture stirred overnight
  3. customReaction mixture
  4. temperaturere-cooled
  5. stirringAfter stirring for 30 mins
  6. concentrationconcentrated
  7. customReaction mixture
  8. stirringstirred overnight
  9. concentrationconcentrated
  10. temperaturewithout heating
  11. customResidue partitioned between DCM and brine
  12. extractionAqueous phase extracted with DCM
  13. customcombined organics dried
  14. concentrationconcentrated
  15. custompurified by chromatography (silica, 0-100% EtOAc-petrol gradient elution)

Sources & evidence

ORD record
ord-6c303eb82da14cdab8b81ffb00d8537c
Source dataset
uspto-grants-2016_04
Patent number
US09309250B2

Reaction notes

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