Methanesulfonamide → HCID 66841258, compound

HRID 244072Notes

Reaction equation

HRID 244072 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[C:13]([C:15]([NH:17][C@H:18]([C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:19][C:20](O)=[O:21])=[O:16])[CH:12]=[CH:11][C:10]=2[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[CH3:33])=[CH:5][C:4]=1[O:34][CH2:35][CH2:36][CH2:37][N:38]([CH3:40])[CH3:39].[CH3:41][S:42]([NH2:45])(=[O:44])=[O:43].CCN=C=NCCCN(C)C.Cl>C(Cl)Cl.CN(C1C=CN=CC=1)C>[ClH:2].[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[C:13]([C:15]([NH:17][C@@H:18]([CH2:19][C:20]([NH:45][S:42]([CH3:41])(=[O:44])=[O:43])=[O:21])[C:23]([CH3:25])([CH3:24])[CH3:26])=[O:16])[CH:12]=[CH:11][C:10]=2[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[CH3:33])=[CH:5][C:4]=1[O:34][CH2:35][CH2:36][CH2:37][N:38]([CH3:40])[CH3:39]

Participants

6

Reactant 3

HCID 72879Methanesulfonamide2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 66840965HCID 66840965, compound

Product 1

HCID 66841258HCID 66841258, compoundYield 93%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 250 mg (0.42 mmol) of (3S)-3-({[6-{4-chloro-3-[3-(dimethylamino)propoxy]phenyl}-5-(2-methylphenyl)pyridin-2-yl]carbonyl}amino)-4,4-dimethylpentanoic acid hydrochloride and 49 mg (0.51 mmol) of methanesulfonamide in 2 mL of DCM are successively added 52 mg (0.42 mmol) of DMAP and 89 mg (0.47 mmol) of EDC.HCl. The reaction medium is stirred for 16 hours at room temperature. A further 0.42 mmol of EDC.HCl and 0.42 mmol of methanesulfonamide are added and the reaction mixture is stirred for a further 3 days and then concentrated under reduced pressure. The residue is taken up in 100 mL of EtOAc and the organic phase is washed with 30 mL of water and then with 30 mL of aqueous 4M NaHCO3 solution. After drying over Na2SO4 and concentrating under reduced pressure, the residue is purified by chromatography on a column of silica gel, eluting with a DCM/methanol gradient of from 0 to 10% methanol. After concentrating under reduced pressure, the residue is taken up in 2 mL of methanol and 0.5 mL of aqueous 1N HCl solution and then purified by reverse-phase HPLC (RP18), eluting with a 10−2N HCl/acetonitrile gradient of from 5% to 100% acetonitrile over 90 minutes. After concentrating under reduced pressure and freeze-drying, 130 mg of 6-{4-chloro-3-[3-(dimethylamino)propoxy]phenyl}-N-[(1S)-2,2-dimethyl-1-{2[(methylsulfonyl)amino]-2-oxoethyl}propyl]-5-(2-methylphenyl)pyridine-2-carboxamide hydrochloride are obtained in the form of a white powder.

Workup

  1. stirringthe reaction mixture is stirred for a further 3 days
  2. concentrationconcentrated under reduced pressure
  3. washthe organic phase is washed with 30 mL of water
  4. dry with materialAfter drying over Na2SO4
  5. concentrationconcentrating under reduced pressure
  6. customthe residue is purified by chromatography on a column of silica gel
  7. washeluting with a DCM/methanol gradient of from 0 to 10% methanol
  8. concentrationAfter concentrating under reduced pressure
  9. custom0.5 mL of aqueous 1N HCl solution and then purified by reverse-phase HPLC (RP18)
  10. washeluting with a 10−2N HCl/acetonitrile gradient of from 5% to 100% acetonitrile over 90 minutes
  11. concentrationAfter concentrating under reduced pressure
  12. customfreeze-drying

Sources & evidence

ORD record
ord-fbc08785ddb943f7a02c13fb296679b4
Source dataset
uspto-grants-2014_02
Patent number
US08653276B2

Reaction notes

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