Methanesulfonyl chloride → HCID 58529765, compound

HRID 1972927Notes

Reaction equation

HRID 1972927 reaction equation
[NH:1]1[CH2:7][CH2:6][CH2:5][CH:4]([C:8]2[N:16]3[C:11]([C:12]([NH2:17])=[N:13][CH:14]=[N:15]3)=[C:10]([C:18]3[CH:19]=[CH:20][C:21]4[C:25]([CH:26]=3)=[N:24][N:23]([CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH:22]=4)[CH:9]=2)[CH2:3][CH2:2]1.[CH3:34][S:35](Cl)(=[O:37])=[O:36].C(N(CC)C(C)C)(C)C>CN(C=O)C>[CH2:27]([N:23]1[CH:22]=[C:21]2[C:25]([CH:26]=[C:18]([C:10]3[CH:9]=[C:8]([CH:4]4[CH2:5][CH2:6][CH2:7][N:1]([S:35]([CH3:34])(=[O:37])=[O:36])[CH2:2][CH2:3]4)[N:16]4[C:11]=3[C:12]([NH2:17])=[N:13][CH:14]=[N:15]4)[CH:19]=[CH:20]2)=[N:24]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 58529755HCID 58529755, compound

Product 1

HCID 58529765HCID 58529765, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 7-azepan-4-yl-5-(2-benzyl-2H-indazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (100 mg, 0.20 mmol) in DMF (1.5 mL) was added methanesulfonyl chloride (17 pt, 0.22 mmol) and N,N-diisopropylethylamine (136 μL, 0.78 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 40% 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 21 mg (21%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 8.53 (s, 1 H), 7.90 (s, 1 H), 7.78 (dd, 1 H), 7.58 (s, 1 H), 7.28-7.38 (m, 5 H), 7.14 (dd, 1 H), 6.61 (s, 1 H), 5.64 (s, 2 H), 3.19-3.56 (m, 4 H), 2.90 (s, 3 H), 1.66-2.20 (m, 7 H); ES-MS m/z 516.30 [M+H]+, HPLC RT (min) 3.07.

Workup

  1. customThe crude mixture was purified by preparative HPLC
  2. washa gradient elution from 15% to 40% 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-0651af96b42b4010b55850713e581804
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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