Potassium Iodide → HCID 58529595, compound

HRID 1972825Notes

Reaction equation

HRID 1972825 reaction equation
[CH2:1]([N:8]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([C:17]3[CH:18]=[C:19]([CH:27]4[O:32][CH2:31][CH:30]5[CH2:33][NH:34][CH2:35][CH2:36][N:29]5[CH2:28]4)[N:20]4[C:25]=3[C:24]([NH2:26])=[N:23][CH:22]=[N:21]4)[CH:13]=[CH:14]2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[I-].[K+].Cl[CH2:46][C:47]([N:49]([CH3:51])[CH3:50])=[O:48]>CN(C=O)C>[NH2:26][C:24]1[C:25]2=[C:17]([C:12]3[CH:13]=[CH:14][C:15]4[C:10]([CH:11]=3)=[N:9][N:8]([CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH:16]=4)[CH:18]=[C:19]([CH:27]3[O:32][CH2:31][CH:30]4[CH2:33][N:34]([CH2:46][C:47]([N:49]([CH3:51])[CH3:50])=[O:48])[CH2:35][CH2:36][N:29]4[CH2:28]3)[N:20]2[N:21]=[CH:22][N:23]=1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 758862-chloro-N,N-dimethylacetamideHCID 58529380HCID 58529380, compound

Product 1

HCID 58529595HCID 58529595, compoundYield 9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

To a stirred solution of 5-(2-benzyl-2H-indazol-6-yl)-7-(octahydropyrazino[2,1-c][1,4]oxazin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (50 mg, 0.10 mmol), K2CO3 (28 mg, 0.21 mmol), and potassium iodide (19 mg, 0.11 mmol) in DMF (1 mL), 2-chloro-N,N-dimethylacetamide (14 mg, 0.11 mmol) was added at rt. The reaction was heated to 65° C. and allowed to stir for 2 hours. The mixture was allowed to cool and partitioned between ethyl acetate (50 mL) and saturated aqueous K2CO3 solution (30 mL). The layers were separated and the organic phase was washed, dried (Na2SO4), and concentrated to dryness. The residue was purified by preparative HPLC using a gradient elution from 10% to 70% acetonitrile to obtain 5 mg (9%) of the desired product. 1H-NMR (DMSO-d6) 8.53 (s, 1H), 7.90 (s, 1H), 7.78 (d, 1H), 7.57 (s, 1H), 7.36 to 7.30 (m, 5H), 7.12 (dd, 1H), 6.71 (s, 1H), 5.64 (s, 2H), 5.09 (dd, 1H), 3.76 (dd, 1H), 3.36-3.27 (m, 1H), 3.11 (d, 2H), 2.99-2.93 (m, 4H), 2.78-2.63 (m, 6H), 2.48-2.36 (m, 1H), 2.24-2.21 (m, 3H), 1.80 (t, 1H); LC-MS [M+H]+=566, RT=2.07 min.

Workup

  1. temperatureto cool
  2. custompartitioned between ethyl acetate (50 mL) and saturated aqueous K2CO3 solution (30 mL)
  3. customThe layers were separated
  4. washthe organic phase was washed
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated to dryness
  7. customThe residue was purified by preparative HPLC
  8. washa gradient elution from 10% to 70% acetonitrile

Sources & evidence

ORD record
ord-fa21b1a470614e71a99d154b27cb033a
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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