Triethylamine → HCID 58529614, compound

HRID 1972899Notes

Reaction equation

HRID 1972899 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[CH2:32][CH2:31][NH:30][CH2:29][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.[CH3:33][S:34](Cl)(=[O:36])=[O:35].C(N(CC)CC)C>ClCCl>[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[CH2:32][CH2:31][N:30]([S:34]([CH3:33])(=[O:36])=[O:35])[CH2:29][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:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 16066662HCID 16066662, compound

Product 1

HCID 58529614HCID 58529614, compoundYield 25.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

To a suspension of 5-(2-benzyl-2H-indazol-6-yl)-7-piperidin-4-ylpyrrolo[2,1-f][1,2,4]triazin-4-amine (80 mg, 0.17 mmol) in dichloromethane (1 mL) was added methanesulfonyl chloride (15 μL, 0.19 mmol) and triethylamine (73 μL, 0.52 mmol). The reaction was stirred at 40° C. for 17 h. The crude mixture was purified by preparative HPLC using a gradient elution from 15% to 50% 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 22 mg (25%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 8.54 (s, 1 H), 7.90 (s, 1 H), 7.80 (d, 1 H), 7.59 (s, 1 H), 7.28-7.39 (m, 5 H), 7.15 (d, 1 H), 6.64 (s, 1 H), 5.65 (s, 2 H), 3.66 (d, 2 H), 3.19-3.30 (m, 1 H), 2.85-2.95 (m, 5 H), 2.11 (d, 2 H), 1.69-1.80 (m, 2 H); ES-MS m/z 502.31 [M+H]+, HPLC RT (min) 2.73.

Workup

  1. customThe crude mixture was purified by preparative HPLC
  2. washa gradient elution from 15% to 50% 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-c42b69a575814c29be74402477689a5c
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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