Sodium borohydride → HCID 86711404, compound

HRID 926334Notes

Reaction equation

HRID 926334 reaction equation
C[O:2][C@@H:3]([C:5]1[N:6]=[CH:7][N:8]([C:10]2[CH:27]=[C:15]3[C:16]4[C:21]([CH2:22][CH2:23][N:14]3[C:13](=[O:28])[CH2:12][N:11]=2)=[C:20]([C:24]([CH3:26])=[CH2:25])[CH:19]=[CH:18][CH:17]=4)[CH:9]=1)[CH3:4].[BH4-].[Na+]>CO.C(Cl)Cl.O>[CH:24]1([C:20]2[CH:19]=[CH:18][CH:17]=[C:16]3[C:21]=2[CH2:22][CH2:23][N:14]2[C:13](=[O:28])[CH2:12][N:11]=[C:10]([N:8]4[CH:9]=[C:5]([CH:3]([OH:2])[CH3:4])[N:6]=[CH:7]4)[CH:27]=[C:15]23)[CH2:26][CH2:25]1

Participants

6

Reactant 2

HCID 4311764Sodium borohydrideHCID 86711397HCID 86711397, compound

Product 1

HCID 86711404HCID 86711404, compoundYield 32.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of 2-(4-acetyl-1H-imidazol-1-yl)-9-cyclopropyl-7,8-dihydro-[1,4]diazepino[7,1-a]isoquinolin-5(4H)-one (202 mg, 0.35 mmol, it can be obtained by analogy to example 118) in MeOH (8 mL) was treated with NaBH4 (27 mg, 0.71 mmol) and the mixture was stirred at RT for 10 min. The mixture was then diluted with DCM and H2O, and the aqueous phase was extracte with DCM. The combined org. layers were dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by SFC (column: PPU 5 m, 250×30 mm, 60 A, Princeton; eluent: 12-17% MeOH/CO2 over 14 min; flow 100 mL/min; UV detection at 220 nm) and crystallization in Et2O gave the title compound as a solid (41 mg). UPLC-MS: MS 363.2 (M+H+); UPLC rt 0.86 min. 1H NMR (600 MHz, DMSO-d6): δ ppm 0.55-0.71 (m, 2H); 0.88-1.02 (m, 2H); 1.35 (d, J=6.40 Hz, 3H); 1.87-2.05 (m, 1H); 2.99-3.17 (m, 2H); 3.79-3.97 (m, 2H); 4.17-4.31 (m, 2H); 4.55-4.71 (m, 1H); 5.01 (d, J=4.89 Hz, 1H); 7.09-7.25 (m, 2H); 7.25-7.39 (m, 1H); 7.46 (s, 1H); 7.84-7.98 (m, 1H); 8.16 (br s, 1H).

Workup

  1. dry with materiallayers were dried over Na2SO4
  2. filtrationfiltered
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by SFC (column: PPU 5 m, 250×30 mm, 60 A, Princeton; eluent: 12-17% MeOH/CO2 over 14 min; flow 100 mL/min; UV detection at 220 nm) and crystallization in Et2O

Sources & evidence

ORD record
ord-878d8e54c6054b078e42d3975e82c8bf
Source dataset
uspto-grants-2016_03
Patent number
US09284331B2

Reaction notes

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