Diisopropylethylamine → 2-(R)-(3-Cyano-benzyl)-3(R)-[4-(6-methoxy-pyridin-3-yl)-benzoylamino]-butyric acid methyl ester

HRID 430898Notes

Reaction equation

HRID 430898 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([C:9]2[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH3:49][O:50][C:51](=[O:65])[C@H:52]([CH2:56][C:57]1[CH:62]=[CH:61][CH:60]=[C:59]([C:63]#[N:64])[CH:58]=1)[C@H:53]([NH2:55])[CH3:54]>CN(C=O)C.CCOC(C)=O>[CH3:49][O:50][C:51](=[O:65])[C@H:52]([CH2:56][C:57]1[CH:62]=[CH:61][CH:60]=[C:59]([C:63]#[N:64])[CH:58]=1)[C@H:53]([NH:55][C:13](=[O:15])[C:12]1[CH:11]=[CH:10][C:9]([C:6]2[CH:7]=[N:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)=[CH:17][CH:16]=1)[CH3:54]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 46742594-(6-methoxypyridin-3-yl)benzoic AcidHCID 154776772(r)-(3-Cyano-benzyl)-3(r)-amino-butyric acid methyl ester

Product 1

HCID 541448392-(R)-(3-Cyano-benzyl)-3(R)-[4-(6-methoxy-pyridin-3-yl)-benzoylamino]-butyric acid methyl esterYield 73.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 4-(6-methoxy-pyridin-3-yl)-benzoic acid (0.67 g, 2.54 mmol) in DMF (5 mL) is added DIPEA (0.44 mL, 2.54 mmol), TBTU (0.91 g, 2.54 mmol) and 2(R)-(3-Cyano-benzyl)-3(R)-amino-butyric acid methyl ester (0.59 g, 2.54 mmol). The solution is stirred overnight at room temperature. The reaction is diluted with EtOAc and washed with saturated sodium bicarbonate (3×), brine, dried over MgSO4, filtered and concentrated. The crude product is purified by flash chromatography (50% EtOAc/hexane to 60% EtOAc/hexane) to give the product as a white solid (0.83 g, 1.87 mmol). 1H NMR (CDCl3, 300 MHz) δ8.43 (d, 1H), 7.92 (d, 2H), 7.83 (dd, 1H), 7.63 (d, 1H), 7.30-7.55 (m, 4H), 6.87 (d, 1H), 4.42-4.53 (m, 1H), 3.98 (s, 3H), 3.66 (s, 3H), 2.85-3.08 (m, 3H), 1.28 (d, 3H).

Workup

  1. washwashed with saturated sodium bicarbonate (3×), brine
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product is purified by flash chromatography (50% EtOAc/hexane to 60% EtOAc/hexane)

Sources & evidence

ORD record
ord-a750528a35a84454869ff9972498fba2
Source dataset
uspto-grants-2001_11
Patent number
US06323227B1

Reaction notes

Loading…