Benzyl Alcohol → 2-(benzyloxy)-N-(5-(1-methyl-1H-indol-2-yl)pyridin-3-yl)ethanesulfonamide

HRID 593689Notes

Reaction equation

HRID 593689 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]([CH3:17])[C:10]3[C:15]([CH:16]=2)=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH:5]=[N:6][CH:7]=1.C(N(CC)CC)C.Cl[CH2:26][CH2:27][S:28](Cl)(=[O:30])=[O:29].[H-].[Na+].[CH2:34]([OH:41])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>C(Cl)Cl>[CH2:34]([O:41][CH2:26][CH2:27][S:28]([NH:1][C:2]1[CH:7]=[N:6][CH:5]=[C:4]([C:8]2[N:9]([CH3:17])[C:10]3[C:15]([CH:16]=2)=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH:3]=1)(=[O:30])=[O:29])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

Participants

7

Reactant 5

HCID 244Benzyl AlcoholHCID 8471TriethylamineHCID 15385Ethanesulfonylchloride, 2-chloro-HCID 24758Sodium hydrideHCID 582155792-(5-amino-pyridin-3-yl)-1-methyl-1H-indole

Product 1

HCID 595346672-(benzyloxy)-N-(5-(1-methyl-1H-indol-2-yl)pyridin-3-yl)ethanesulfonamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 5-(1-methyl-1H-indol-2-yl)pyridin-3-amine (Example 100, 150 mg, 0.672 mmol) and triethylamine (272 mg, 2.69 mmol) in DCM (6 mL) is added 2-chloroethanesulfonyl chloride (274 mg, 1.68 mmol) in DCM (2 mL) dropwise at 0° C. The mixture is stirred at 0° C. for 1 h. Silica gel (5 g) is added and the mixture is concentrated. After elution, the fractions containing the product are concentrated to give a residue, which is redissolved in benzyl alcohol (20 mL). 60% NaH in mineral oil is added. The mixture is stirred at 70° C. for 1 day. The mixture is then filtered and the filtrate is purified on Xbridge C18 eluting with a 1:9 to 9:1 acetonitrile-water gradient to give 2-(benzyloxy)-N-(5-(1-methyl-1H-indol-2-yl)pyridin-3-yl)ethanesulfonamide. MS (ESI) m/z 422.1 (M+H)+.

Workup

  1. additionSilica gel (5 g) is added
  2. concentrationthe mixture is concentrated
  3. washAfter elution
  4. additionthe fractions containing the product
  5. concentrationare concentrated
  6. customto give a residue, which
  7. stirringThe mixture is stirred at 70° C. for 1 day
  8. filtrationThe mixture is then filtered
  9. customthe filtrate is purified on Xbridge
  10. washC18 eluting with a 1:9 to 9:1 acetonitrile-water gradient

Sources & evidence

ORD record
ord-cbd2c51b00f54875929dcd13ee6672eb
Source dataset
uspto-grants-2016_01
Patent number
US09242963B2

Reaction notes

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