4-Methylmorpholine → HCID 10449448, compound

HRID 1796871Notes

Reaction equation

HRID 1796871 reaction equation
C(OC([NH:8][C@H:9]([CH2:15][CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)[CH:10]([OH:14])[C:11]([OH:13])=[O:12])=O)(C)(C)C.N[C@H:23]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH2:25][C@H:24]1O.Cl.C[N:35](C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.CN1CCOCC1>ClCCl.ClCCl.CN(C=O)C>[NH2:8][C@H:9]([CH2:15][CH:16]1[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]1)[CH:10]([OH:14])[C:11]([O:13][C@H:23]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH2:25][C@H:24]1[NH2:35])=[O:12]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 9866743(1S,2R)-(-)-1-Amino-2-indanolHCID 69588616HCID 69588616, compound

Product 1

HCID 10449448HCID 10449448, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

A solution of Example 3C (0.10 g, 0.33 mmol), (1S,2R)-1-amino-2-hydroxyindane (0.086 g, 0.58 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.080 g, 0.41 mmol), 1-hydroxybenzotriazole (0.061 g, 0.45 mmol), and N-methylmorpholine (0.05 mL, 0.46 mmol) in 3:1 dichloromethane/DMF (4 mL) at room temperature was stirred for 16 hours, diluted with dichloromethane, washed sequentially with aqueous NaHCO3, brine, 10% KHSO4, and brine, dried (MgSO4), filtered, and concentrated. The residue was dissolved in 4M HCl in dioxane (3 mL), stirred for 1 hour, concentrated, then purified by reverse phase HPLC with acetonitrile/water to provide the desired product. MS (ESI) m/e 333 (M+H)+; 1H NMR (300 MHz, DMSO-d6) δ 7.81 (br s, 2H), 7.40–7.17 (m, 4H), 6.65 (d, 1H), 5.52 (m, 1H), 4.18 (d, 1H), 3.14 (m, 1H), 2.55–2.45 (m, 2H), 1.80–1.67 (m, 5H), 1.57–1.51 (m, 1H), 1.46–1.17 (m, 5H), 1.00–0.90 (m, 2H).

Workup

  1. washwashed sequentially with aqueous NaHCO3, brine, 10% KHSO4, and brine
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in 4M HCl in dioxane (3 mL)
  6. concentrationconcentrated
  7. custompurified by reverse phase HPLC with acetonitrile/water

Sources & evidence

ORD record
ord-14646cbf95cc499ea9d0c8fc5c7c36ac
Source dataset
uspto-grants-2006_04
Patent number
US07030262B2

Reaction notes

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