Triethylamine → N-[3-amino-2-methoxy-5-(1-methyl-cyclopropyl)-phenyl]-methanesulfonamide

HRID 2099148Notes

Reaction equation

HRID 2099148 reaction equation
C(N(CC)CC)C.[CH3:8][O:9][C:10]1[C:15]([NH2:16])=[CH:14][C:13]([C:17]2([CH3:20])[CH2:19][CH2:18]2)=[CH:12][C:11]=1[NH2:21].[CH3:22][S:23](Cl)(=[O:25])=[O:24]>C(Cl)Cl>[NH2:21][C:11]1[C:10]([O:9][CH3:8])=[C:15]([NH:16][S:23]([CH3:22])(=[O:25])=[O:24])[CH:14]=[C:13]([C:17]2([CH3:20])[CH2:19][CH2:18]2)[CH:12]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 179730872-Methoxy-5-(1-methyl-cyclopropyl)-benzene-1,3-diamine

Product 1

HCID 22025264N-[3-amino-2-methoxy-5-(1-methyl-cyclopropyl)-phenyl]-methanesulfonamideYield 51%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Triethylamine (521 μL, 3.74 mmol) was added to a solution of 2-methoxy-5-(1-methyl-cyclopropyl)-benzene-1,3-diamine (718 mg, 3.74 mmol) in methylene chloride at −10° C. Methanesulfonyl chloride (290 μL, 3.74 mmol) was then added dropwise over a 10 min period and the resultant solution was allowed to slowly warm to rt over 2 h. The mixture was quenched with saturated aqueous NaHCO3 and the aqueous layer was extracted with methylene chloride. The combined organic layers were dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography (1% ammonium hydroxide/35% ethyl acetate in hexanes to 1% ammonium hydroxide/50% ethyl acetate in hexanes) provided a red solid which was triturated with a diethyl ether/hexanes (1:1) to yield Compound 1 (510 mg, 51%) as a pale brown solid: mp 144-146° C. ESI MS (m/z 271, M+H).

Workup

  1. customThe mixture was quenched with saturated aqueous NaHCO3
  2. extractionthe aqueous layer was extracted with methylene chloride
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by silica gel chromatography (1% ammonium hydroxide/35% ethyl acetate in hexanes to 1% ammonium hydroxide/50% ethyl acetate in hexanes)
  7. customprovided a red solid which
  8. customwas triturated with a diethyl ether/hexanes (1:1)

Sources & evidence

ORD record
ord-a9e59ae5231b4eb1b678169a09619b6a
Source dataset
uspto-grants-2009_08
Patent number
US07569568B2

Reaction notes

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