Methanesulfonamide → HCID 66657392, compound

HRID 420486Notes

Reaction equation

HRID 420486 reaction equation
[CH2:1]([N:3]([CH3:32])[C:4]1[N:5]=[C:6]([NH:24][C:25]2[CH:30]=[C:29]([CH3:31])[CH:28]=[CH:27][N:26]=2)[C:7]2[N:12]([CH2:13][CH2:14][O:15][CH2:16][C:17]([F:20])([F:19])[F:18])[N:11]=[C:10]([C:21]([OH:23])=O)[C:8]=2[N:9]=1)[CH3:2].Cl.CN(C)CCCN=C=NCC.[CH3:45][S:46]([NH2:49])(=[O:48])=[O:47]>CN(C)C1C=CN=CC=1.ClCCl.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[CH2:1]([N:3]([CH3:32])[C:4]1[N:5]=[C:6]([NH:24][C:25]2[CH:30]=[C:29]([CH3:31])[CH:28]=[CH:27][N:26]=2)[C:7]2[N:12]([CH2:13][CH2:14][O:15][CH2:16][C:17]([F:18])([F:19])[F:20])[N:11]=[C:10]([C:21]([NH:49][S:46]([CH3:45])(=[O:48])=[O:47])=[O:23])[C:8]=2[N:9]=1)[CH3:2]

Participants

7

Reactant 3

HCID 72879MethanesulfonamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57799220HCID 57799220, compound

Product 1

HCID 66657392HCID 66657392, compound

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 311Citric AcidSolventHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of the chloride from preparation 261 (50 mg, 0.1 mmol), N-ethyldiisopropylamine (0.05 mL, 0.3 mmol), N-ethylmethylamine (0.026 mL, 0.3 mmol) and cesium fluoride (15 mg, 0.1 mmol) in 1-methyl-2-pyrrolidinone (1 mL) was heated in a Reactivial® at 110° C. for 90 minutes. The cooled reaction mixture was purified directly using a Phenomenex Luna C18 column reverse phase column and acetonitrile:95% water/5% methanol/0.1% trifluoroacetic acid (5:95 to 95:5) as elution gradient. The product was dissolved in dichloromethane and the solution washed with sodium bicarbonate solution, dried over magnesium sulphate and evaporated under reduced pressure to provide the title compound, 24 mg. Alternatively, example 178 may be prepared by the method of examples 172-177. 4-Dimethylaminopyridine (22 mg, 0.20 mmol) was added to a solution of the acid from example 127 (70 mg, 0.15 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (38 mg, 0.20 mmol) and methanesulphonamide (19 mg, 0.20 mmol) in dichloromethane (2 ml) and the reaction stirred at room temperature for 18 hours. The mixture was diluted with dichloromethane (20 mls) and 1M citric acid solution (10 ml), then the phases separated. The organic phase was purified directly by column chromatography on silica gel (using a Parallel Flashmaster system) using an elution gradient of methanol:dichloromethane (0:100 to 2:98) to provide the title compound as a yellow solid. 1H NMR (DMSO-D6+1 drop TFAd, 400 MHz) δ: 1.19 (t, 3H), 2.49 (s, 3H), 3.20 (s, 3H), 3.41 (s, 3H), 3.66 (q, 2H), 4.06 (q, 2H), 4.14 (t, 2H), 5.03 (t, 2H), 7.20 (d, 1H), 8.12 (s, 1H), 8.27 (d, 1H). MS ES− m/z 529 [M-H]−

Workup

  1. customAlternatively, example 178 may be prepared by the method of examples 172-177
  2. customthe phases separated
  3. customThe organic phase was purified directly by column chromatography on silica gel (

Sources & evidence

ORD record
ord-5213cebc1a424d8f819b89efcb183960
Source dataset
uspto-grants-2012_01
Patent number
US08097621B2

Reaction notes

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