Methanesulfonyl chloride → HCID 58529319, compound

HRID 1972953Notes

Reaction equation

HRID 1972953 reaction equation
Cl.[NH:2]1[CH2:5][CH:4]([CH2:6][C:7]2[N:15]3[C:10]([C:11]([NH2:16])=[N:12][CH:13]=[N:14]3)=[C:9]([C:17]3[CH:18]=[CH:19][C:20]4[C:24]([CH:25]=3)=[N:23][N:22]([CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH:21]=4)[CH:8]=2)[CH2:3]1.[CH3:33][S:34](Cl)(=[O:36])=[O:35].C(N(CC)C(C)C)(C)C>CN(C=O)C>[CH2:26]([N:22]1[CH:21]=[C:20]2[C:24]([CH:25]=[C:17]([C:9]3[CH:8]=[C:7]([CH2:6][CH:4]4[CH2:5][N:2]([S:34]([CH3:33])(=[O:36])=[O:35])[CH2:3]4)[N:15]4[C:10]=3[C:11]([NH2:16])=[N:12][CH:13]=[N:14]4)[CH:18]=[CH:19]2)=[N:23]1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 69304364HCID 69304364, compound

Product 1

HCID 58529319HCID 58529319, compoundYield 17.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution 7-(azetidin-3-ylmethyl)-5-(2-benzyl-2H-indazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine hydrochloride (100 mg, 0.22 mmol) in DMF (1.5 mL) was added methanesulfonyl chloride (19 μL, 0.25 mmol) and N,N-diisopropylethylamine (117 μL, 0.67 mmol). The reaction was stirred at rt for 17 h. The crude mixture was purified by preparative HPLC using a gradient elution from 15% to 45% acetonitrile in water followed by filtration through an acidic resin, washing with MeOH. The product was eluted with 2M NH3 in MeOH and the filtrate was concentrated to provide 19 mg (17%) of the desired product. 1H NMR (400 MHz, DMSO-da) δ 8.54 (s, 1 H), 7.90 (s, 1 H), 7.79 (d, 1 H), 7.58 (s, 1 H), 7.25-7.37 (m, 5 H), 7.13 (dd, 1 H), 6.66 (s, 1 H), 5.64 (s, 2 H), 3.97 (t, 2 H), 3.69 (dd, 2 H), 3.14-3.19 (m, 2 H), 2.97-3.98 (m, 1 H), 2.96 (s, 3 H); ES-MS m/z 5488.38 [M+H]+, HPLC RT (min) 2.98.

Workup

  1. customThe crude mixture was purified by preparative HPLC
  2. washa gradient elution from 15% to 45% acetonitrile in water
  3. filtrationfollowed by filtration through an acidic resin
  4. washwashing with MeOH
  5. washThe product was eluted with 2M NH3 in MeOH
  6. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-17cf8999f5f8432c9ab80af795f03054
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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