Acetyl chloride → HCID 58529745, compound

HRID 1972969Notes

Reaction equation

HRID 1972969 reaction equation
[NH2:1][C:2]1[N:3]([CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[N:4]=[C:5]2[C:10]=1[CH:9]=[CH:8][C:7]([C:11]1[CH:12]=[C:13]([CH:21]3[CH2:26][CH2:25][N:24]([S:27]([CH3:30])(=[O:29])=[O:28])[CH2:23][CH2:22]3)[N:14]3[C:19]=1[C:18]([NH2:20])=[N:17][CH:16]=[N:15]3)=[CH:6]2.[C:38](Cl)(=[O:40])[CH3:39]>ClCCCl.N1C=CC=CC=1>[NH2:20][C:18]1[C:19]2=[C:11]([C:7]3[CH:8]=[CH:9][C:10]4[C:5]([CH:6]=3)=[N:4][N:3]([CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[C:2]=4[NH:1][C:38](=[O:40])[CH3:39])[CH:12]=[C:13]([CH:21]3[CH2:26][CH2:25][N:24]([S:27]([CH3:30])(=[O:29])=[O:28])[CH2:23][CH2:22]3)[N:14]2[N:15]=[CH:16][N:17]=1

Participants

5

Reactant 2

HCID 6367Acetyl chlorideHCID 58529399HCID 58529399, compound

Product 1

HCID 58529745HCID 58529745, compoundYield 9%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 1049PyridineSolvent

Procedure

To a suspension of 5-(3-Amino-2-benzyl-2H-indazol-6-yl)-7-(1-methanesulfonyl-piperidin-4-yl)-pyrrolo[2,1-f][1,2,4]triazin-4-ylamine (150 mg, 0.29 mmol) in DCE (2.9 mL) and pyridine (0.29 mL) was added acetyl chloride (20 μl, 0.38 mmol, 1.3 mmol), and the reaction mixture was stirred at rt under N2 for 18 h. The mixture was partitioned between EtOAc and water. The organic phase was washed with water and brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude was purified via preparative HPLC. The product containing fractions were collected, and the TFA from the eluent was removed via filtration through an acidic resin followed by washing with acetonitrile. The product was then eluted with 2M NH3 in MeOH. The MeOH was removed and the residue was crystallized from DCM-hexane to provide the title compound (14 mg, 9%) as a solid. 1H NMR (300 MHz, DMSO-d6) δ 10.34 (s, 1H), 7.91 (s, 1H), 7.58 (d, 1H), 7.51 (s, 1H), 7.35 to 7.22 (m, 5H), 7.14 (dd, 1H), 6.65 (s, 1H), 5.49 (s, 2H), 3.68 to 3.64 (m, 2H), 3.26 (dt, 1H), 2.92 to 2.86 (m, 5H), 2.16 to 2.07 (m, 5H), 1.77 to 1.73 (m, 2H); ES-MS m/z 559.4 [M+H]+, RT (min) 2.39.

Workup

  1. customThe mixture was partitioned between EtOAc and water
  2. washThe organic phase was washed with water and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude was purified via preparative HPLC
  7. additionThe product containing fractions
  8. customwere collected
  9. customthe TFA from the eluent was removed via filtration through an acidic resin
  10. washby washing with acetonitrile
  11. washThe product was then eluted with 2M NH3 in MeOH
  12. customThe MeOH was removed
  13. customthe residue was crystallized from DCM-hexane

Sources & evidence

ORD record
ord-c771f0606b484f618082b5562c56109d
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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