Lithium Hydroxide → HCID 22730282, compound

HRID 2356134Notes

Reaction equation

HRID 2356134 reaction equation
CO[C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH2:12][CH2:13][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:15][CH:16]=2)=[CH:7][CH:6]=1)=[O:4].[Li+].[OH-].[N+:26]([C:29]1[CH:30]=[C:31]([S:45]([NH2:48])(=[O:47])=[O:46])[CH:32]=[CH:33][C:34]=1[NH:35][CH2:36][CH2:37][S:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)([O-:28])=[O:27].CCN=C=NCCCN(C)C>C1COCC1.CO.CN(C1C=CN=CC=1)C.ClC(Cl)C.C(OCC)(=O)C.O>[N+:26]([C:29]1[CH:30]=[C:31]([S:45]([NH:48][C:3]([C:5]2[CH:10]=[CH:9][C:8]([C:11]3[CH2:12][CH2:13][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:15][CH:16]=3)=[CH:7][CH:6]=2)=[O:4])(=[O:46])=[O:47])[CH:32]=[CH:33][C:34]=1[NH:35][CH2:36][CH2:37][S:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)([O-:28])=[O:27]

Participants

11

Reactant 4

HCID 3939Lithium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 8461424HCID 8461424, compoundHCID 22730763HCID 22730763, compound

Product 1

HCID 22730282HCID 22730282, compound

Reagents, catalysts & solvents 6

HCID 142844-(Dimethylamino)pyridineCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 63651,1-DichloroethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of Example 455B (1 g, 3.1 mmol) and LiOH (0-264 mg 6.2 mmol) in THF (15 mL), methanol (2.5 mL), and water (1.5 mL) was heated to 50° C. for 3 hours and concentrated. The concentrate was dissolved in DMF (10 mL) and treated with a mixture of Example 77B (1.059 g, 3 mmol), EDCI (1.146 g, 6 mmol), and DMAP (1.830, 15 mmol) in dichloroethane (10 mL), stirred for 16 hours, diluted with ethyl acetate (250 mL), washed sequentially with 1N HCl (50 mL, water (100 mL) and brine (100 mL), dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 5% methanol/dichloromethane to provide the desired product. MS (ESI(−)) m/e 637 (M−H)−; 1H NMR (300 MHz, DMSO-d6) δ 8.78 (br t, 1H), 8.60 (d, 1H), 7.92 (dd, 1H), 7.85 (d, 2H), 7.55 (d, 2H), 7.40-7.15 (m, 6H), 6.35 (m, 1H), 4.21 (d, 2H), 3.65 (m, 2H), 3.52 (t, 2H), 3.25 (m, 4H), 1.45 (s, 9H).

Workup

  1. concentrationconcentrated
  2. dissolutionThe concentrate was dissolved in DMF (10 mL)
  3. washwashed sequentially with 1N HCl (50 mL, water (100 mL) and brine (100 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe concentrate was purified by flash column chromatography on silica gel with 5% methanol/dichloromethane

Sources & evidence

ORD record
ord-1d3ced85df9943319db3696667881c24
Source dataset
uspto-grants-2010_07
Patent number
US07754886B2

Reaction notes

Loading…