Dimethylformamide → HCID 73335341, compound

HRID 532910Notes

Reaction equation

HRID 532910 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]1[C:16](=[O:17])[CH2:15][N:14]=[C:13]([C:18]3[S:19][CH:20]=[CH:21][CH:22]=3)[CH:12]=[C:7]12.[CH3:23][N:24](C=O)C>CCOC(C)=O.[C-]#N.[C-]#N.[Zn+2].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>[O:17]=[C:16]1[N:6]2[CH2:5][CH2:4][C:3]3[C:2]([C:23]#[N:24])=[CH:11][CH:10]=[CH:9][C:8]=3[C:7]2=[CH:12][C:13]([C:18]2[S:19][CH:20]=[CH:21][CH:22]=2)=[N:14][CH2:15]1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 73335237HCID 73335237, compound

Product 1

HCID 73335341HCID 73335341, compound

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
170 °C

Procedure

A microwave flask was charged with 9-bromo-2-(thiophen-2-yl)-7,8-dihydro-[1,4]diazepino[7,1-a]isoquinolin-5(4H)-one (Example 29) (145 mg, 0.39 mmol), Zn(CN)2 (191 mg, 1.63 mmol) and Pd(PPh3)4 (47 mg, 0.041 mmol) in DMF (4 mL) was heated to 170° C. for 18 h. The reaction was allowed to cool to RT, taken up in AcOEt and washed iwth H2O. The org. layer was dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography (SiO2, hexane to hexan/AcOEt 1:1) and prep. HPLC (column: RP-C18 sunfire, 5 μm, 100×300 mm; solvent A: H2O+0.1% TFA; solvent B CH3CN; gradient (% B): 10-30% in 16 min; 50 mL/min). The product obtained was passed onto a SPE cartridge to release the free base, and the residue obtained was triturated in heptane/AcOEt to give the title compound (8 mg) as a yellow solid. UPLC-MS: MS 320.2 (M+H+); UPLC rt 0.87 min. 1H NMR (600 MHz, DMSO-d6): δ ppm 3.07 (t, J=5.55 Hz, 2 H); 3.87 (br. s., 2 H); 4.29 (br. s., 2 H); 7.11 (t, J=4.14 Hz, 1 H); 7.51 (s, 1 H); 7.56 (t, J=7.87 Hz, 1 H); 7.66 (d, J=4.24 Hz, 2 H); 7.93 (d, J=7.47 Hz, 1 H); 8.42 (d, J=8.07 Hz, 1 H).

Workup

  1. temperatureto cool to RT
  2. washwashed iwth H2O
  3. dry with materiallayer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash chromatography (SiO2, hexane to hexan/AcOEt 1:1)
  7. customThe product obtained
  8. customthe residue obtained
  9. customwas triturated in heptane/AcOEt

Sources & evidence

ORD record
ord-d0befb3ae1bb4bd08181c682feda92a8
Source dataset
uspto-grants-2014_10
Patent number
US08853203B2

Reaction notes

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