Isopropanol → HCID 67367771, compound

HRID 1753149Notes

Reaction equation

HRID 1753149 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]23[NH:20][CH2:19][CH2:18][N:9]2[C:10](=[O:17])[C:11]2[N:12]([CH:14]=[CH:15][CH:16]=2)[CH2:13]3)=[CH:4][CH:3]=1.[CH3:21][N:22](C=O)C.C([O-])(O)=O.[Na+].CC(O)C>C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C-]#N.[C-]#N.[Zn+2].CO>[O:17]=[C:10]1[N:9]2[CH2:18][CH2:19][NH:20][C:8]2([C:5]2[CH:6]=[CH:7][C:2]([C:21]#[N:22])=[CH:3][CH:4]=2)[CH2:13][N:12]2[CH:14]=[CH:15][CH:16]=[C:11]12

Participants

9

Reactant 4

HCID 3776IsopropanolHCID 6228DimethylformamideHCID 516892Sodium BicarbonateHCID 67371585HCID 67371585, compound

Product 1

HCID 67367771HCID 67367771, compound

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst2×HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
140 °C

Procedure

10a-(4-bromophenyl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (50 mg, 0.15 mmol), tetrakis(triphenylphosphine)palladium(0) (8.7 mg, 7.5 μmol), Zn(CN)2 (27 mg, 0.23 mmol), and DMF (2 mL) were added to a microwave reaction vial that was sealed under argon. The reaction mixture was heated in a microwave reactor at 140° C. for 20 min, resulting in a dark yellow mixture. The reaction mixture was heated for a further 20 min at 150° C. LCMS analysis showed a mixture of target product (279 m/z) and starting bromo core (332/334 m/z). Another portion of tetrakis(triphenylphosphine)palladium (0) (8.7 mg, 7.5 μmol) was added and the mixture heated at 160° C. The reaction went to completion after 20 min. A saturated aqueous solution of NaHCO3 (50 mL) was added and CH2Cl2 containing 20% of propan-2-ol (50 mL). The organic layer was separated, dried (MgSO4) and concentrated in vacuo to give crude product that was purified using flash chromatography (Biotage SP4, 12 g cartridge; 0-10% MeOH gradient in CH2Cl2 to give 4-(5-oxo-2,3-dihydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-10a(10H)-yl)benzonitrile as a brown crystalline solid (48.5 mg, quantitative yield). 1H NMR (400 MHz, d6-acetone): δ 3.07-3.41 (m, 1H), 3.44 (ddd, 1H, J 10.9, 7.8, 3.2 Hz), 3.48-3.61 (m, 1H), 3.72 (dt, 1H, J 10.8, 7.9 Hz), 4.41 (d, 1H, J 12.5 Hz), 4.72 (d, 1H, J 12.5 Hz), 6.04 (dd, 1H, J 3.8, 2.6 Hz), 6.65-6.67 (m, 1H), 6.70 (dd, 1H, J 3.7, 1.5 Hz), 7.55-7.73 (m, 4H). The product was used in the next step without further purification.

Workup

  1. customthat was sealed under argon
  2. customresulting in a dark yellow mixture
  3. temperatureThe reaction mixture was heated for a further 20 min at 150° C
  4. additiona mixture of target product (279 m/z)
  5. temperaturethe mixture heated at 160° C
  6. customThe organic layer was separated
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customto give crude product that
  10. customwas purified

Sources & evidence

ORD record
ord-b3e04d67bf4546e3b3f418c9ded53f05
Source dataset
uspto-grants-2015_10
Patent number
US09163029B2

Reaction notes

Loading…