Hydrochloric Acid → HCID 89980374, compound

HRID 926286Notes

Reaction equation

HRID 926286 reaction equation
[C:1]([C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH2:6][CH2:7][N:8]1[C:18](=[O:19])[CH2:17][N:16]=[C:15]([C:20]3[CH:24]=[CH:23][N:22]([CH3:25])[N:21]=3)[CH:14]=[C:9]12)(=[O:3])[CH3:2].I[C:27]1C=CC=C2C=1CCN1C(=O)CN=C(C3C=CN(C)N=3)C=C12.C([Sn](CCCC)(CCCC)C(OCC)=C)CCC.Cl>O1CCOCC1.C1COCC1.CCOC(C)=O.CCOCC.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>[CH3:27][O:3][CH:1]([C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH2:6][CH2:7][N:8]1[C:18](=[O:19])[CH2:17][N:16]=[C:15]([C:20]3[CH:24]=[CH:23][N:22]([CH3:25])[N:21]=3)[CH:14]=[C:9]12)[CH3:2]

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 86711358HCID 86711358, compoundHCID 86711359HCID 86711359, compound

Product 1

HCID 89980374HCID 89980374, compound

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

9-acetyl-2-(1-methyl-1H-pyrazol-3-yl)-7,8-dihydro-[1,4]diazepino[7,1-a]isoquinolin-5(4H)-one. 47-1. A mixture of 9-iodo-2-(1-methyl-1H-pyrazol-3-yl)-7,8-dihydro-[1,4]diazepino[7,1-a]isoquinolin-5(4H)-one (Example 31) (2.0 g, 4.78 mmol), tributyl(1-ethoxyvinyl)stannane (2.02 mL, 5.98 mmol) and Pd(PPh3)4 (276 mg, 0.24 mmol) in 1,4-dioxane (15 mL) was heated to 140° C. for 90 min. The mixture was then filtered and concentrated in vacuo and the residue obtained was purified by flash chromatography (SiO2, DCM to DCM/MeOH 95:5). The brown oil obtained was taken up in THF (100 mL) and treated with a 0.1 N aq. solution of HCl (48 mL, 4.78 mmol). The mixture was stirred at RT for 90 min. The mixture was then diluted with AcOEt and washed with a saturated aq. solution of NaHCO3. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The residue obtained was purified by flash chromatography (SiO2, DCM to DCM/MeOH 95:5) to give a brown oil that was suspended in Et2O. The suspension was filtered and the filter cake was dried in vacuo to give the title compound (912 mg) as a yellow solid. UPLC-MS: MS 335.0 (M+H+); UPLC rt 0.62 min. 1H NMR (400 MHz, CHLOROFORM-d): δ ppm 2.62 (s, 3 H); 3.24 (t, J=6.06 Hz, 2 H); 3.81 (t, J=6.45 Hz, 2 H); 3.92 (s, 3 H); 4.49 (br. s., 2 H); 6.81 (br. s., 1 H); 7.17 (s, 1 H); 7.34-7.45 (m, 2 H); 7.77 (d, J=7.82 Hz, 1 H); 7.84 (d, J=7.82 Hz, 1 H).

Workup

  1. filtrationThe mixture was then filtered
  2. concentrationconcentrated in vacuo
  3. customthe residue obtained
  4. customwas purified by flash chromatography (SiO2, DCM to DCM/MeOH 95:5)
  5. customThe brown oil obtained
  6. washwashed with a saturated aq. solution of NaHCO3
  7. dry with materialThe organic layer was dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue obtained
  11. customwas purified by flash chromatography (SiO2, DCM to DCM/MeOH 95:5)
  12. customto give a brown oil that
  13. filtrationThe suspension was filtered
  14. customthe filter cake was dried in vacuo

Sources & evidence

ORD record
ord-9399f14638484fafa2cb8d1ddc9ce8b4
Source dataset
uspto-grants-2016_03
Patent number
US09284331B2

Reaction notes

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