Sodium cyanoborohydride → HCID 11292964, compound

HRID 1831922Notes

Reaction equation

HRID 1831922 reaction equation
[Cl:1][C:2]1[C:3](=[O:29])[N:4]([CH2:18][C:19]2[CH:28]=[CH:27][CH:26]=[C:25]3[C:20]=2[CH:21]=[CH:22][N:23]=[CH:24]3)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].[BH3-]C#N.[Na+]>CC(O)=O.O.[OH-].[Na+]>[Cl:1][C:2]1[C:3](=[O:29])[N:4]([CH2:18][C:19]2[CH:28]=[CH:27][CH:26]=[C:25]3[C:20]=2[CH2:21][CH2:22][NH:23][CH2:24]3)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17]

Participants

6

Reactant 2

HCID 5003444Sodium cyanoborohydrideHCID 11212109HCID 11212109, compound

Product 1

HCID 11292964HCID 11292964, compoundYield 92%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-chloro-4-(2,4-difluorobenzyloxy)-1-isoquinolin-5-ylmethyl-1H-pyridin-2-one (Example 84) (0.14 g, 0.34 mmol) in AcOH (1.3 mL) was added NaCNBH3 (0.09 g, 1.4 mmol), and the reaction mixture was stirred for 2 h. The reaction mixture was cooled to 0° C., and diluted with water(10 mL) and 40% aqueous NaOH (10 mL), and the aqueous layer was washed with EtOAc (3×50 mL). The combined organics were washed with brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, eluent 98:1.8:0.2 to 88:10.8:1.2 CH2Cl2/MeOH/NH3) provided 3-chloro-4-(2,4-difluoro-benzyloxy)-1-(1,2,3,4-tetrahydroisoquinolin-5-ylmethyl)-1H-pyridin-2-one as a white solid (0.13 g, 92%): mp 180-184° C.; 1H NMR (300 MHz, MeOD) δ 7.65-7.55 (m, 2H), 7.16-7.00 (m, 4H), 6.90-6.80 (m, 1H), 6.60 (d, J=8 Hz, 1H), 5.31 (s, 2H), 5.20 (s, 2H), 4.06 (s, 2H), 3.21 (t, J=6 Hz, 2H), 2.82 (t, J=6 Hz, 2H). ES HRMS m/z 417.1173 (M+H C22H20ClF2N2O2 requires 417.1176).

Workup

  1. washthe aqueous layer was washed with EtOAc (3×50 mL)
  2. washThe combined organics were washed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by flash column chromatography (silica, eluent 98:1.8:0.2 to 88:10.8:1.2 CH2Cl2/MeOH/NH3)

Sources & evidence

ORD record
ord-139ad58a8e2a4b818541a0134acd99e3
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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