Sodium borohydride → HCID 67439654, compound

HRID 1483672Notes

Reaction equation

HRID 1483672 reaction equation
[CH3:1][N:2]([CH3:29])[C:3]1[N:10]=[C:9]([O:11][C:12]2[CH:17]=[CH:16][C:15]([B:18]3[O:22]C(C)(C)C(C)(C)O3)=[C:14]([CH:27]=[O:28])[CH:13]=2)[CH:8]=[CH:7][C:4]=1[C:5]#[N:6].[BH4-].[Na+]>C(Cl)Cl.CO>[CH3:29][N:2]([CH3:1])[C:3]1[N:10]=[C:9]([O:11][C:12]2[CH:17]=[CH:16][C:15]3[B:18]([OH:22])[O:28][CH2:27][C:14]=3[CH:13]=2)[CH:8]=[CH:7][C:4]=1[C:5]#[N:6]

Participants

5

Reactant 2

HCID 4311764Sodium borohydride2×HCID 86636423HCID 86636423, compound

Product 1

HCID 67439654HCID 67439654, compoundYield 198.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 2-dimethylamino-6-[3-formyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenoxy]-nicotinonitrile (7) (370 mg, 0.94 mmol) in CH2Cl2 (5 mL) was added to a mixture of NaBH4 (26 mg, 0.66 mmol) in anhydrous methanol (10 mL) at room temperature. Additional solid NaBH4 (82 mg, 2.2 mmol) was then added portionwise over a period of 10 minutes. The reaction mixture was then stirred for a further 1 h at room temperature. The reaction was quenched by the addition of a solution of glacial acetic acid (0.2 mL) and distilled water (0.2 mL) followed by stirring for 10 minutes. The reaction was concentrated to give an oil (˜550 mg). The oil was dissolved in a mixture of acetic acid/methanol/CH2Cl2 (1/2/100 v/v/v, 100 mL) followed by the addition of silica gel (5 g, 230-400 mesh) and concentrated to dryness to give a free flowing impregnated silica. This was loaded onto a silica column (10 g, 230-400 mesh) and eluted with acetic acid/methanol/CH2Cl2 (1/2/100 v/v/v). The fractions containing D95 were collected and concentrated to give a light yellow coloured oil. The oil was freeze dried by first diluting with MeOH/CH2Cl2 (1/1 v/v, 15 mL) followed by the addition of deionised water (200 mL), the resultant white suspension was frozen in a dry-ice acetone bath and placed overnight on freeze-dryer. A white solid of D95 was obtained (70 mg, 25% isolated yield). 1H NMR 400 MHz (d6-DMSO) δ9.23 (s, 1H), 7.95 (d, J=8.6 Hz, 1H), 7.77 (d, J=7.8 Hz, 1H), 7.23 (d, J=0.5 Hz, 1H), 7.16 (dd, J=7.8, 0.5 Hz, 1H), 6.31 (d, J=8.6 Hz, 1H), 4.98 (s, 2H), 3.14 (s, 6H). Mass Spectrum [M+H+]=296. HPLC purity 95.04% (Maxplot), 94.63% (220 nm), 92.41% (254 nm).

Workup

  1. customThe reaction was quenched by the addition of a solution of glacial acetic acid (0.2 mL)
  2. distillationdistilled water (0.2 mL)
  3. stirringby stirring for 10 minutes
  4. concentrationThe reaction was concentrated

Sources & evidence

ORD record
ord-22b591961614425d9125c2449c613f64
Source dataset
uspto-grants-2016_08
Patent number
US09416146B2

Reaction notes

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