1,2-Dichloroethane → Methyl (2r)-3-[(4-{[(4-tert-butylcyclohexyl)(1-methyl-1h-benzimidazol-2-yl)amino]-methyl}benzoyl)amino]-2-hydroxypropanoate

HRID 229990Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 229990
[C:1]([CH:5]1[CH2:10][CH2:9][CH:8]([N:11]([CH2:22][C:23]2[CH:31]=[CH:30][C:26]([C:27](O)=[O:28])=[CH:25][CH:24]=2)[C:12]2[N:16]([CH3:17])[C:15]3[CH:18]=[CH:19][CH:20]=[CH:21][C:14]=3[N:13]=2)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[CH3:32][O:33][C:34](=[O:39])[CH:35]([OH:38])[CH2:36][NH2:37].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C>CN(C=O)C>[C:1]([CH:5]1[CH2:6][CH2:7][CH:8]([N:11]([CH2:22][C:23]2[CH:24]=[CH:25][C:26]([C:27]([NH:37][CH2:36][C@@H:35]([OH:38])[C:34]([O:33][CH3:32])=[O:39])=[O:28])=[CH:30][CH:31]=2)[C:12]2[N:16]([CH3:17])[C:15]3[CH:18]=[CH:19][CH:20]=[CH:21][C:14]=3[N:13]=2)[CH2:9][CH2:10]1)([CH3:4])([CH3:2])[CH3:3]

Komponenten

7

Edukt 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 11105589Methyl 3-amino-2-hydroxypropanoateHCID 688367154-{[(4-tert-Butylcyclohexyl)(1-methyl-1H-benzimidazol-2-yl)amino]methyl}-benzoic acid

Produkt 1

HCID 57758784Methyl (2r)-3-[(4-{[(4-tert-butylcyclohexyl)(1-methyl-1h-benzimidazol-2-yl)amino]-methyl}benzoyl)amino]-2-hydroxypropanoate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of the title compound of Example 5 Step A (0.32 mmol, 145 mg), the hydrochloride salt of 2-hydroxy β-alanine methyl ester (0.48 mmol, 74 mg), HOBt (0.8 mmol, 121 mg) and EDC (0.96 mmol, 183 mg) in 2 mL of DMF was added DIEA (1.6 mmol, 0.28 mL). After 3 h the reaction was partitioned into EtOAc/brine. The organic phase was dried with MgSO4 and concentrated under reduced pressure. The product was purified by flash chromatography on silica eluting with 1:25:74 MeOH/EtOAc/DCM, affording the title compound as a foamy solid. 1HNMR (500 MHz, DMSO-d6): δ 8.47 (t, 1H), 7.75 (d, 2H), 7.60 (m, 1H), 7.48 (m, 1H), 7.45 (d, 2H), 7.30-7.37 (overlapping m, 2H), 4.80 (s, 2H), 3.76 (s, 3H), 3.70 (m, 1H), 3.60 (s, 3H), 3.50 (m, 1H), 3.39 (m, 1H), 2.02 (m, 2H), 1.82 (m, 2H), 1.71 (m, 2H), 1.18 (m, 2H), 1.03 (m, 1H), 0.85 (s, 9H). MS (ESI): m/z 521 (M+H). HPLC A: 1.94 min.

Aufarbeitung

  1. customAfter 3 h the reaction was partitioned into EtOAc/brine
  2. dry with materialThe organic phase was dried with MgSO4
  3. concentrationconcentrated under reduced pressure
  4. customThe product was purified by flash chromatography on silica eluting with 1:25:74 MeOH/EtOAc/DCM

Quellen und Nachweise

ORD-Eintrag
ord-7efb78a9e5bd48df9338056dbeebced7
Quelldatensatz
uspto-grants-2009_07
Patentnummer
US07563815B2

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