Acetic acid, azido-, ethyl ester → HCID 71280804, compound

HRID 1497932Notes

Reaction equation

HRID 1497932 reaction equation
[F:1][C:2]1([F:32])[CH2:5][CH:4]([C:6]2[O:10][N:9]=[C:8]([C:11]3[CH:12]=[CH:13][C:14]([CH3:31])=[C:15]([NH:17][C:18]([C:20]4[N:24]5[CH:25]=[CH:26][C:27]([C:29]#[CH:30])=[CH:28][C:23]5=[N:22][CH:21]=4)=[O:19])[CH:16]=3)[N:7]=2)[CH2:3]1.[N:33]([CH2:36][C:37](OCC)=[O:38])=[N+:34]=[N-:35].O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+].[BH4-].[Na+]>CC(O)(C)C.O.CO.[O-]S([O-])(=O)=O.[Cu+2]>[F:32][C:2]1([F:1])[CH2:5][CH:4]([C:6]2[O:10][N:9]=[C:8]([C:11]3[CH:12]=[CH:13][C:14]([CH3:31])=[C:15]([NH:17][C:18]([C:20]4[N:24]5[CH:25]=[CH:26][C:27]([C:29]6[N:35]=[N:34][N:33]([CH2:36][CH2:37][OH:38])[CH:30]=6)=[CH:28][C:23]5=[N:22][CH:21]=4)=[O:19])[CH:16]=3)[N:7]=2)[CH2:3]1

Participants

8

Reactant 4

HCID 69480Acetic acid, azido-, ethyl esterHCID 4311764Sodium borohydrideHCID 23667548Sodium AscorbateHCID 86677526HCID 86677526, compound

Product 1

HCID 71280804HCID 71280804, compound

Reagents, catalysts & solvents 3

HCID 24462Copper SulfateCatalystHCID 887MethanolSolventHCID 714019492-Methylpropan-2-ol--water (1/1)Solvent

Procedure

A mixture of N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-ethynylimidazo[1,2-a]pyridine-3-carboxamide (53) (20 mg, 0.046 mmol), ethyl 2-azidoacetate (5.9 mg, 0.046 mmol), CuSO4(4 μL of 0.5M aqueous solution, 0.002 mmol) and sodium ascorbate (2.8 mg, 0.014 mmol) in tBuOH/H2O (1 mL, 2:1) was stirred at room temperature overnight. Then the reaction mixture was diluted and extracted with EtOAc. The organic layers were combined, dried over Na2SO4, filtered and concentrated to afford a residue which was dissolved in MeOH (2 mL). NaBH4(17 mg, 0.46 mmol) was added and the reaction mixture was stirred for 30 minutes. The above mixture was purified by HPLC to give N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-(1-(2-hydroxyethyl)-1H-1,2,3-triazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (F66). 1H NMR (400 MHz, d4-MeOH) δ 9.70 (m, 1H), 8.60-8.80 (m, 2H), 8.33 (s, 1H), 8.16 (d, J=1.6 Hz, 1H), 7.96 (m, 1H), 7.85 (d, J=7.2 Hz, 1H), 7.50 (d, J=8.0 Hz, 1H), 4.62 (t, J=4.8 Hz, 2H), 4.02 (t, J=4.8 Hz, 2H), 3.79 (m, 1H), 3.13 (m, 4H), 2.44 (s, 3H). MS m/z 521.1 (M+1)+.

Workup

  1. additionThen the reaction mixture was diluted
  2. extractionextracted with EtOAc
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto afford a residue which
  7. stirringthe reaction mixture was stirred for 30 minutes
  8. customThe above mixture was purified by HPLC

Sources & evidence

ORD record
ord-fcca7ccf1020473ab11caca01c858b22
Source dataset
uspto-grants-2015_12
Patent number
US09199981B2

Reaction notes

Loading…