Methylamine → HCID 66864635, compound

HRID 2093431Notes

Reaction equation

HRID 2093431 reaction equation
O[N:2]1[C:6]2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.CN.[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]([C:56]2[CH:61]=[CH:60][C:59]([Cl:62])=[CH:58][CH:57]=2)[N:33]2[CH2:36][CH:35]([CH2:37][S:38]([NH:41][C:42]3[CH:43]=[C:44]([CH:53]=[CH:54][CH:55]=3)[C:45]([NH:47][C@@H:48]([CH3:52])[C:49](O)=[O:50])=[O:46])(=[O:40])=[O:39])[CH2:34]2)=[CH:28][CH:27]=1>O1CCCC1.C(N(CC)CC)C>[Cl:62][C:59]1[CH:58]=[CH:57][C:56]([CH:32]([C:29]2[CH:28]=[CH:27][C:26]([Cl:25])=[CH:31][CH:30]=2)[N:33]2[CH2:36][CH:35]([CH2:37][S:38]([NH:41][C:42]3[CH:43]=[C:44]([CH:53]=[CH:54][CH:55]=3)[C:45]([NH:47][C@H:48]([C:49](=[O:50])[NH:2][CH3:6])[CH3:52])=[O:46])(=[O:40])=[O:39])[CH2:34]2)=[CH:61][CH:60]=1

Participants

7

Reactant 4

HCID 6329MethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66864198HCID 66864198, compound

Product 1

HCID 66864635HCID 66864635, compoundYield 111.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8471TriethylamineSolvent

Conditions

Temperature
20 °C

Procedure

60 mg of 1-hydroxybenzotriazole, 200 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 0.700 cm3 of a 2M solution of methylamine in tetrahydrofuran, 0.370 cm3 of triethylamine and 8 cm3 of tetrahydrofuran are added successively to a solution of 0.5 g of (S)-2-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}methanesulphonylamino)benzoyl-amino]propionic acid in 15 cm3 of tetrahydrofuran, stirred at a temperature in the region of 20° C. under an inert atmosphere. The reaction medium is stirred at a temperature in the region of 20° C. for 18 hours. After concentration to dryness under reduced pressure, the residue is dissolved in a mixture consisting of 30/15 cm3 of dichloromethane/water. After separation by settling out, the aqueous phase is extracted twice with 15 cm3 of dichloromethane. The organic phases are combined, washed with 15 cm3 of a saturated aqueous solution of sodium chloride, dried over magnesium sulphate, filtered and then concentrated to dryness, to give 0.415 g of a crude product which is purified by flash chromatography on a Merck 25 g silica cartridge (particle size: 15-40 μm; eluent: 100 ethyl acetate). After concentration of the fractions under reduced pressure, 0.293 g of a product is obtained which is triturated in a minimum amount of pentane. After filtration, concentration to dryness under reduced pressure and drying, 0.247 g of a solid cream is obtained. 147 mg of this solid cream are injected onto a column 6 cm in diameter containing 700 g of Chiralpak IA 20 μM chiral stationary phase. The elution is carried out at 80 cm3 per minute with a mobile phase composed of 95% acetonitrile and 5% dichloromethane. The dextrorotatory enantiomer is eluted in the second position. After concentration of the mobile phase, 105 mg of 3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}methanesulphonylamino)-N—((S)-1-methyl-carbamoylethyl)benzamide are obtained in the form of an amorphous white powder.

Workup

  1. stirringThe reaction medium is stirred at a temperature in the region of 20° C. for 18 hours
  2. concentrationAfter concentration to dryness under reduced pressure
  3. dissolutionthe residue is dissolved in a mixture
  4. customAfter separation
  5. extractionthe aqueous phase is extracted twice with 15 cm3 of dichloromethane
  6. washwashed with 15 cm3 of a saturated aqueous solution of sodium chloride
  7. dry with materialdried over magnesium sulphate
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. customto give 0.415 g of a crude product which
  11. customis purified by flash chromatography on a Merck 25 g silica cartridge (particle size: 15-40 μm; eluent: 100 ethyl acetate)

Sources & evidence

ORD record
ord-08375a33d9004903b71e15467af61735
Source dataset
uspto-grants-2013_05
Patent number
US08445478B2

Reaction notes

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