Cyclopropanecarboxaldehyde → HCID 118022050, compound

HRID 575599Notes

Reaction equation

HRID 575599 reaction equation
[NH2:1][C:2]1[C:7](=[O:8])[N:6]([CH3:9])[CH:5]=[C:4]([C:10]2[CH:11]=[CH:12][C:13]([O:21][CH3:22])=[C:14]([NH:16][S:17]([CH3:20])(=[O:19])=[O:18])[CH:15]=2)[CH:3]=1.[CH:23]1([CH:26]=O)[CH2:25][CH2:24]1.[BH3-]C#N.[Na+]>CO.CC(O)=O>[CH:23]1([CH2:26][NH:1][C:2]2[C:7](=[O:8])[N:6]([CH3:9])[CH:5]=[C:4]([C:10]3[CH:11]=[CH:12][C:13]([O:21][CH3:22])=[C:14]([NH:16][S:17]([CH3:20])(=[O:19])=[O:18])[CH:15]=3)[CH:3]=2)[CH2:25][CH2:24]1

Participants

6

Reactant 3

HCID 123114CyclopropanecarboxaldehydeHCID 5003444Sodium cyanoborohydrideHCID 118021572HCID 118021572, compound

Product 1

HCID 118022050HCID 118022050, compoundYield 13.2%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Conditions

Temperature
30 °C

Procedure

To a solution of compound from Example 109 (64.6 mg, 0.2 mmol) in MeOH (3 mL) and AcOH (0.3 mL) was added cyclopropanecarbaldehyde (14.0 mg, 0.2 mmol) dropwise with stirring at 30° C. NaBH3CN (24.5 mg, 0.4 mol) was added in portions at 30° C. The reaction mixture was stirred for 2 h at 30° C. It was then quenched with saturated aqueous NH4Cl (5 mL), extracted with EtOAc (20 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by prep-HPLC to give the title compound (10.0 mg, 13.2%) as a light green solid. 1H NMR (Methanol-d4 400 MHz): δ 7.55 (d, J=2.4 Hz, 1H), 7.36 (dd, J=8.4, 2.4 Hz, 1H), 7.16-7.07 (m, 2H), 6.61 (d, J=2.4 Hz, 1H), 3.94 (s, 3H), 3.66 (s, 3H), 3.05 (s, 2H), 2.95 (s, 3H), 1.21-1.14 (m, 1H), 0.64-0.56 (m, 2H), 0.35-0.28 (m, 2H). LCMS (M+H)+ 378.

Workup

  1. stirringThe reaction mixture was stirred for 2 h at 30° C
  2. customIt was then quenched with saturated aqueous NH4Cl (5 mL)
  3. extractionextracted with EtOAc (20 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-8acf373c4ace40cb971a8ddcb9eb18e8
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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