Acetyl chloride → HCID 58529867, compound

HRID 1972888Notes

Reaction equation

HRID 1972888 reaction equation
Cl.[NH2:2][C:3]1[C:8]2=[C:9]([C:19]3[CH:20]=[CH:21][C:22]4[C:26]([CH:27]=3)=[N:25][N:24]([CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH:23]=4)[CH:10]=[C:11]([C:12]([CH:14]3[CH2:18][CH2:17][NH:16][CH2:15]3)=[O:13])[N:7]2[N:6]=[CH:5][N:4]=1.C([O-])([O-])=O.[Na+].[Na+].[C:41](Cl)(=[O:43])[CH3:42]>CC#N.CO>[NH2:2][C:3]1[C:8]2=[C:9]([C:19]3[CH:20]=[CH:21][C:22]4[C:26]([CH:27]=3)=[N:25][N:24]([CH2:28][C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH:23]=4)[CH:10]=[C:11]([C:12]([CH:14]3[CH2:18][CH2:17][N:16]([C:41](=[O:43])[CH3:42])[CH2:15]3)=[O:13])[N:7]2[N:6]=[CH:5][N:4]=1

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 10340Sodium CarbonateHCID 69327098HCID 69327098, compound

Product 1

HCID 58529867HCID 58529867, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 21959252Acetonitrile methanolSolvent

Procedure

[4-Amino-5-(2-benzyl-2H-indazol-6-yl)-pyrrolo[2,1-f][1,2,4]triazin-7-yl]-pyrrolidin-3-yl-methanone hydrochloride salt (80 mg, 0.17 mmol) was dissolved in CH3CN/MeOH (1:1, 2 mL) and 2N Na2CO3 (0.84 mL, 1.68 mmol) was added, followed by acetyl chloride (0.013 mL, 0.19 mmol). The resulting mixture was stirred at rt for 12 h. The mixture was concentrated, diluted with EtOAc and layers were separated. The organic layer was washed with brine and concentrated. The residue was purified by short silica-gel column eluting with EtOAc, then 10% MeOH in EtOAc to give 39 mg (48%) of the desired product. 1H-NMR (CD3OD-d4) 8.39-8.35 (m, 1H), 8.03 (d, 1H), 7.81 (dt, 1H), 7.69-7.67 (m, 1 H), 7.47 (d, 1H), 7.37-7.27, (m, 5 H), 7.19 (fit, 1 H), 5.64 (s, 1 H), 4.53-4.38 (m, 1 H), 3.92-3.72 (m, 2 H), 3.62 (t, 1H), 3.52 (t, 1 H), 2.38-2.07 (m, 2 H), 2.10 (d, 3 H); LC-MS [M+H]+=480.1, RT=2.64 min.

Workup

  1. concentrationThe mixture was concentrated
  2. additiondiluted with EtOAc and layers
  3. customwere separated
  4. washThe organic layer was washed with brine
  5. concentrationconcentrated
  6. customThe residue was purified by short silica-gel column
  7. washeluting with EtOAc

Sources & evidence

ORD record
ord-25b102c4b23e47bbaadc2be27efef42a
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

Loading…