Hydrochloric Acid → HCID 58052498, compound

HRID 2190193Notes

Reaction equation

HRID 2190193 reaction equation
C[O:2][C:3](=[O:36])[CH:4]=[CH:5][CH2:6][CH2:7][N:8]([C:13]1[N:18]=[C:17]2[O:19][C:20]([C:26]3[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=3)=[C:21]([C:22](=[O:25])[NH:23][CH3:24])[C:16]2=[CH:15][C:14]=1[CH:33]1[CH2:35][CH2:34]1)[S:9]([CH3:12])(=[O:11])=[O:10].[CH3:37][NH:38][CH3:39].[Li+].[OH-].Cl>C(Cl)Cl.C1COCC1.O.CO>[CH:33]1([C:14]2[CH:15]=[C:16]3[C:21]([C:22](=[O:25])[NH:23][CH3:24])=[C:20]([C:26]4[CH:27]=[CH:28][C:29]([CH3:32])=[CH:30][CH:31]=4)[O:19][C:17]3=[N:18][C:13]=2[N:8]([S:9]([CH3:12])(=[O:11])=[O:10])[CH2:7][CH2:6][CH:5]([N:38]([CH3:39])[CH3:37])[CH2:4][C:3]([OH:2])=[O:36])[CH2:35][CH2:34]1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 674DimethylamineHCID 3939Lithium HydroxideHCID 66663337HCID 66663337, compound

Product 1

HCID 58052498HCID 58052498, compoundYield 21.7%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-[(5-cyclopropyl-3-methylcarbamoyl-2-p-tolyl-furo[2,3-b]pyridin-6-yl)-methanesulfonyl-amino]-pent-2-enoic acid methyl ester (26 mg, 0.051 mmol, 1.0 equiv) in DCM (0.5 mL) was added dimethyl amine (0.10 mL, 2.0 M in THF, 0.2 mmol, 4.0 equiv) and LiClO4 (10.8 mg, 0.1 mmol, 2.0 equiv). The mixture was stirred at room temperature for 24 hours. The reaction mixture was then diluted with THF (0.3 mL), water (0.3 mL), MeOH (0.3 mL) and to the solution was added LiOH (4.9 mg, 0.2 mmol, 5.0 equiv). The mixture was heated at 55° C. for 20 minutes. The solution was neutralized to pH=7 by addition of 1.0 N HCl aq. solution. The mixture was extracted with CH2Cl2. The organic layer was dried over Na2SO4 and concentrated. The residue was purified by reverse phase HPLC with ammonium hydroxide as modifier to give product 6.0 mg. MS (ESI) m/z 543.6 (M+1). Retention time=1.09 min, Method A. 1H NMR (400 MHz, MeOD) d ppm 0.77-0.92 (m, 2H) 1.09-1.20 (m, 2H) 1.61-1.75 (m, 1 H) 2.00-2.11 (m, 1H) 2.37-2.47 (m, 4H) 2.48-2.58 (m, 2H) 2.68 (s, 6H) 2.93 (s, 3 H) 3.17 (s, 3H) 3.51-3.62 (m, 1H) 3.82-3.94 (m, 1H) 3.94-4.04 (m, 1H) 7.35 (d, J=8.03 Hz, 2H) 7.59 (s, 1H) 7.79 (d, J=8.53 Hz, 2H)

Workup

  1. temperatureThe mixture was heated at 55° C. for 20 minutes
  2. extractionThe mixture was extracted with CH2Cl2
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by reverse phase HPLC with ammonium hydroxide as modifier

Sources & evidence

ORD record
ord-d041a6cff66447408bd8d0406ef90b90
Source dataset
uspto-grants-2012_12
Patent number
US08324239B2

Reaction notes

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