Lithium Hydroxide → HCID 22730282, compound

HRID 1785848Notes

Reaction equation

HRID 1785848 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, 3mmol), 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 mL0, 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-f393d314843f45daae93ff7e9eb80178
Source dataset
uspto-grants-2009_03
Patent number
US07504512B2

Reaction notes

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