1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (2R,4S)-ethyl 5-(biphenyl-4-yl)-4-(2-methoxythiazole-5-carboxamido)-2-methylpentanoate

HRID 1469686Notes

Reaction equation

HRID 1469686 reaction equation
[CH3:1][O:2][C:3]1[S:4][C:5]([C:8]([OH:10])=O)=[CH:6][N:7]=1.C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[NH2:33][C@H:34]([CH2:43][C:44]1[CH:49]=[CH:48][C:47]([C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)=[CH:46][CH:45]=1)[CH2:35][C@@H:36]([CH3:42])[C:37]([O:39][CH2:40][CH3:41])=[O:38]>CN(C=O)C>[C:47]1([C:50]2[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=2)[CH:46]=[CH:45][C:44]([CH2:43][C@@H:34]([NH:33][C:8]([C:5]2[S:4][C:3]([O:2][CH3:1])=[N:7][CH:6]=2)=[O:10])[CH2:35][C@@H:36]([CH3:42])[C:37]([O:39][CH2:40][CH3:41])=[O:38])=[CH:49][CH:48]=1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 181649HOAtHCID 164948972-Methoxy-1,3-thiazole-5-carboxylic acidHCID 25017086(2R,4S)-4-amino-5-(biphenyl-4-yl)-2-methylpentanoic acid ethyl ester hydrochloride

Product 1

HCID 59608216(2R,4S)-ethyl 5-(biphenyl-4-yl)-4-(2-methoxythiazole-5-carboxamido)-2-methylpentanoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-methoxythiazole-5-carboxylic acid (101 mg, 0.64 mmol) in DMF (6 mL) is added HOAt (107 mg, 0.58 mmol), EDCI (133 mg, 0.69 mmol), and TEA (0.48 mL, 3.47 mmol). The crude is stirred at room temperature for 15 mins. To this crude is added (2R,4S)-ethyl 4-amino-5-(biphenyl-4-yl)-2-methylpentanoate hydrochloride salt. The crude is stirred at room temperature for overnight. The crude is quenched with 1 N HCl and water, diluted in EtOAc. The organic layer is washed with brine, dried over MgSO4, filtered, and concentrated. The residue is purified via flash column chromatography using 30% EtOAc/heptane to 70% EtOAc/heptane to give (2R,4S)-ethyl 5-(biphenyl-4-yl)-4-(2-methoxythiazole-5-carboxamido)-2-methylpentanoate (170 mg). HPLC retention time 1.94 minutes (condition A); MS 453.3 (M+1); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.18 (d, J=7.1 Hz, 3 H), 1.23 (t, J=7.1 Hz, 3 H), 1.71 (ddd, J=14.0, 9.9, 3.9 Hz, 1 H), 1.88-2.04 (m, 1 H), 2.56-2.73 (m, 1 H), 2.78-2.96 (m, 1 H), 2.96-3.09 (m, 1 H), 4.09 (s, 3 H), 4.09-4.18 (m, 2 H), 4.30-4.47 (m, 1 H), 6.15 (d, J=8.1 Hz, 1 H), 7.27 (d, J=6.8 Hz, 2 H), 7.29-7.36 (m, 1 H), 7.42 (t, J=7.6 Hz, 2 H), 7.49 (s, 1 H), 7.53 (d, J=8.1 Hz, 2 H), 7.57 (d, J=7.3 Hz, 2 H).

Workup

  1. stirringThe crude is stirred at room temperature for overnight
  2. customThe crude is quenched with 1 N HCl and water
  3. additiondiluted in EtOAc
  4. washThe organic layer is washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue is purified via flash column chromatography

Sources & evidence

ORD record
ord-02813670ac2c43538e5e809bf9c06ce2
Source dataset
uspto-grants-2015_04
Patent number
US09006249B2

Reaction notes

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