Methylamine hydrochloride → HCID 67334932, compound

HRID 1850007Notes

Reaction equation

HRID 1850007 reaction equation
Br[C:2]([CH3:16])([CH3:15])[C:3]([NH:5][C:6]1[O:10][N:9]=[C:8]([C:11]([CH3:14])([CH3:13])[CH3:12])[CH:7]=1)=[O:4].Cl.[CH3:18][NH2:19]>ClC(Cl)C>[C:11]([C:8]1[CH:7]=[C:6]([NH:5][C:3](=[O:4])[C:2]([NH:19][CH3:18])([CH3:16])[CH3:15])[O:10][N:9]=1)([CH3:14])([CH3:13])[CH3:12]

Participants

4

Reactant 2

HCID 6364545Methylamine hydrochlorideHCID 59703982HCID 59703982, compound

Product 1

HCID 67334932HCID 67334932, compoundYield 58.5%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of 2-bromo-N-(3-tert-butyl-isoxazol-5-yl)-2-methyl-propionamide (prepared according to method B, step 1, 1.45 g, 1.5 mmol) in anhydrous dichloroethane (25 mL) are added methylamine hydrochloride (0.66 g, 10.0 mmol) and 1,8-diazabicyclo[5.40]undec-7-ene (3.81 g, 25.0 mmol). The reaction is heated to 85° C. for 16 h. After cooling the reaction mixture to ambient temperature it was washed with saturated NaHCO3 (25 mL). The water layer was extracted with dichloromethane (25 mL). The combined organic layers were dried over MgSO4, filtered and the filtrate is concentrated under reduced pressure. The crude product is purified by chromatography on silica eluting with 0% to 10% methanol/DCM to provide N-(3-tert-butyl-isoxazol-5-yl)-2-methylamino-2-methyl-propionamide (0.21 g, 17%). To a solution of N-(3-tert-butyl-isoxazol-5-yl)-2-methylamino-propionamide (36 mg, 0.15 mmol) in anhydrous dichloroethane (1 mL) are added N-methylmorpholine (82 μL, 0.75 mmol) and 4-chlorobenzenesulfonyl chloride (63 mg, 0.30 mmol). The reaction is concentrated under reduced pressure to give a yellow oil, which is purified by mass-triggered preparative HPLC to afford N-(5-tert-Butyl-isoxazol-3-yl)-2-[(4-chloro-benzenesulfonyl)-methyl-amino]-2-methyl-propionamide (32 mg, 52%). m/z 414 [M+H+]

Workup

  1. temperatureAfter cooling the reaction mixture to ambient temperature it
  2. washwas washed with saturated NaHCO3 (25 mL)
  3. extractionThe water layer was extracted with dichloromethane (25 mL)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationthe filtrate is concentrated under reduced pressure
  7. customThe crude product is purified by chromatography on silica eluting with 0% to 10% methanol/DCM

Sources & evidence

ORD record
ord-530a21a3dd104ab2b357327245ec29ec
Source dataset
uspto-grants-2015_02
Patent number
US08957063B2

Reaction notes

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