Sodium cyanoborohydride → rac-2-(4-ethyl-1H-imidazol-1-yl)-9-(1-hydroxyethyl)-7,8-dihydro-[1,4]diazepino[7,1-a]isoquinolin-5(4H)-one

HRID 532953Notes

Reaction equation

HRID 532953 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]([N:20]3[CH:24]=[C:23]([CH2:25][CH3:26])[N:22]=[CH:21]3)[CH:14]=[C:9]12)(=[O:3])[CH3:2].[BH3-]C#N.[Na+]>CO.C(Cl)Cl>[CH2:25]([C:23]1[N:22]=[CH:21][N:20]([C:15]2[CH:14]=[C:9]3[C:10]4[C:5]([CH2:6][CH2:7][N:8]3[C:18](=[O:19])[CH2:17][N:16]=2)=[C:4]([CH:1]([OH:3])[CH3:2])[CH:13]=[CH:12][CH:11]=4)[CH:24]=1)[CH3:26]

Participants

5

Reactant 2

HCID 5003444Sodium cyanoborohydrideHCID 867113959-acetyl-2-(4-ethyl-1H-imidazol-1-yl)-7,8-dihydro-[1,4]diazepino[7,1-a]isoquinolin-5(4H)-one

Product 1

HCID 73336024rac-2-(4-ethyl-1H-imidazol-1-yl)-9-(1-hydroxyethyl)-7,8-dihydro-[1,4]diazepino[7,1-a]isoquinolin-5(4H)-oneYield 4.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

Example 115. A solution of 9-acetyl-2-(4-ethyl-1H-imidazol-1-yl)-7,8-dihydro-[1,4]diazepino[7,1-a]isoquinolin-5(4H)-one (210 mg, 0.36 mmol) in MeOH (20 mL) was treated with NaBH3CN (23 mg, 0.36 mmol) and the mixture was stirred at RT for 10 min. The mixture was then concentrated in vacuo and the residue obtained was taken up in DCM and washed with H2O. The org layer was then dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography (SiO2, heptane to AcOEt to AcOEt/MeOH 85:15) and preparative TLC (SiO2, DCM/MeOH 95:5) afforded the title compound (6 mg). UPLC-MS: MS 351.2 (M+H+); UPLC rt 0.65 min. 1H NMR (400 MHz, CD3OD): δ ppm 1.16-1.27 (m, 3 H); 1.44 (d, J=6.26 Hz, 3 H); 2.58 (q, J=7.56 Hz, 2 H); 2.97-3.17 (m, 2 H); 3.80 (m, 1 H); 3.88-4.00 (m, 2 H); 4.31-4.36 (m, 2 H); 5.14 (d, J=6.65 Hz, 1 H); 6.95 (s, 1 H); 7.34 (s, 1 H); 7.37-7.49 (m, 1 H); 7.67 (d, J=7.43 Hz, 1 H); 7.77 (d, J=7.82 Hz, 1 H); 8.11 (s, 1 H).

Workup

  1. concentrationThe mixture was then concentrated in vacuo
  2. customthe residue obtained
  3. washwashed with H2O
  4. dry with materialThe org layer was then dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by flash chromatography (SiO2, heptane to AcOEt to AcOEt/MeOH 85:15) and preparative TLC (SiO2, DCM/MeOH 95:5)

Sources & evidence

ORD record
ord-eca669e8590c42ed95083da781f3caf9
Source dataset
uspto-grants-2014_10
Patent number
US08853203B2

Reaction notes

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