Sodium borohydride → HCID 58798986, compound

HRID 2117128Notes

Reaction equation

HRID 2117128 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:26][C:27](=[O:39])[CH2:28][C:29]([NH:31][C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=2)=[O:30])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:14]2=[C:15]([CH:18]=[C:19]3[CH2:24][CH2:23][C:22](=[O:25])[CH2:21][CH2:20]3)[CH:16]=[CH:17][N:13]2[N:12]=[CH:11][N:10]=1.[BH4-].[Na+]>CO>[F:1][C:2]1[CH:3]=[C:4]([NH:26][C:27](=[O:39])[CH2:28][C:29]([NH:31][C:32]2[CH:33]=[CH:34][C:35]([F:38])=[CH:36][CH:37]=2)=[O:30])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:14]2=[C:15]([CH:18]=[C:19]3[CH2:24][CH2:23][CH:22]([OH:25])[CH2:21][CH2:20]3)[CH:16]=[CH:17][N:13]2[N:12]=[CH:11][N:10]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 58799045HCID 58799045, compound

Product 1

HCID 58798986HCID 58798986, compoundYield 37.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

To N1-(3-fluoro-4-(5-((4-oxocyclohexylidene)methyl)pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)phenyl)-N3-(4-fluorophenyl)malonamide (80 mg, 0.15 mmol, Example 149) in methanol (2 mL) at 0° C. was added a spatula tip of sodium borohydride. The reaction was stirred at 0° C. for 30 min and was then quenched with saturated aqueous ammonium chloride solution (10 mL) and stirred at 0° C. for 5 min. The mixture was extracted with ethyl acetate (3×10 mL) and the combined organic extracts were dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel (10% MeOH/EtOAc) to give the title compound (30 mg, 37%) as an off-white solid. 1H NMR (DMSO-d6) δ 10.57 (s, 1H), 10.34 (s, 1H), 8.11 (d, 1H, J=2.8 Hz), 8.10 (s, 1H), 7.86 (dd, 1H, J=12.8, 2.4 Hz), 7.71-7.68 (m, 2H), 7.53 (t, 1H, J=8.4 Hz), 7.46-7.43 (m, 1H), 7.25-7.21 (m, 2H), 6.99 (d, 1H, J=2.8 Hz), 6.64 (s, 1H), 4.65 (br s, 1H), 3.76-3.75 (m, 1H), 3.56 (s, 2H), 2.90-2.85 (m, 1H), 2.51-2.45 (m, 1H), 2.27-2.24 (m, 2H), 1.92-1.85 (m, 2H), 1.46-1.41 (m, 2H); MS(ESI+) m/z 534.3 (M+H)+.

Workup

  1. customwas then quenched with saturated aqueous ammonium chloride solution (10 mL)
  2. stirringstirred at 0° C. for 5 min
  3. extractionThe mixture was extracted with ethyl acetate (3×10 mL)
  4. dry with materialthe combined organic extracts were dried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash chromatography on silica gel (10% MeOH/EtOAc)

Sources & evidence

ORD record
ord-471c29edc39f419fafbcf3217e5f13fb
Source dataset
uspto-grants-2008_10
Patent number
US07439246B2

Reaction notes

Loading…