Lithium Hydroxide → HCID 10119718, compound

HRID 2355999Notes

Reaction equation

HRID 2355999 reaction equation
[C:1]([CH:5]1[CH2:10][CH2:9][CH:8]([C:11]2[CH:20]=[CH:19][C:14]([C:15]([O:17]C)=O)=[CH:13][CH:12]=2)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[Li+].[OH-].[CH:23]1([NH:29][C:30]2[CH:35]=[CH:34][C:33]([S:36]([NH2:39])(=[O:38])=[O:37])=[CH:32][C:31]=2[N+:40]([O-:42])=[O:41])[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1.CCN=C=NCCCN(C)C>C1COCC1.CN(C1C=CN=CC=1)C.O1CCOCC1.C(OCC)(=O)C>[C:1]([CH:5]1[CH2:6][CH2:7][CH:8]([C:11]2[CH:20]=[CH:19][C:14]([C:15]([NH:39][S:36]([C:33]3[CH:34]=[CH:35][C:30]([NH:29][CH:23]4[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]4)=[C:31]([N+:40]([O-:42])=[O:41])[CH:32]=3)(=[O:38])=[O:37])=[O:17])=[CH:13][CH:12]=2)[CH2:9][CH2:10]1)([CH3:3])([CH3:4])[CH3:2]

Participants

9

Reactant 4

HCID 3939Lithium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 22660807HCID 22660807, compoundHCID 22730084HCID 22730084, compound

Product 1

HCID 10119718HCID 10119718, compound

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of Example 5C (55 mg, 0.20 mmol) and 1M LiOH (0.3 mL) in THF (2 mL) was heated to 50° C., stirred for 3 hours, concentrated, dissolved in DMF (0.5 mL), and treated with a mixture of Example 3A (60 mg, 0.20 mmol), EDCI (96 mg, 0.50 mmol), and DMAP (10 mg) in dioxane (2.0 mL). The mixture was stirred for 16 hours, diluted with ethyl acetate (50 mL), washed sequentially with 1M HCl (5 mL), water (5 mL), and brine (5 mL), dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel, with 50% ethyl acetate/hexanes to provide a ˜2:1 mixture of diastereomers. MS (ESI(−)) m/e 540 (M−H)−; 1H NMR (400 MHz, DMSO-d6) δ 8.63 (2d, 1H total), 8.33 (2d, 1H total), 7.95 (m, 1H), 7.82 and 7.78 (2d, 2H total), 7.45 (m, 1H), 7.30 (m, 2H), 3.71 (m, 1H), 2.28-0.95 (m, 20H), 0.86 and 0.75 (2s, 9H total).

Workup

  1. concentrationconcentrated
  2. dissolutiondissolved in DMF (0.5 mL)
  3. stirringThe mixture was stirred for 16 hours
  4. washwashed sequentially with 1M HCl (5 mL), water (5 mL), and brine (5 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe concentrate was purified by flash column chromatography on silica gel, with 50% ethyl acetate/hexanes
  9. customto provide
  10. additiona ˜2:1 mixture of diastereomers

Sources & evidence

ORD record
ord-fac8088bf15d4b7f94206eb9b80469cc
Source dataset
uspto-grants-2010_07
Patent number
US07754886B2

Reaction notes

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