1,2-Dichloroethane → (2S)-tert-Butyl 2-((2S)-2-(2-(5-formylthiazol-2-ylamino)-3-methylbutanamido)propanamido)propanoate

HRID 1755446Notes

Reaction equation

HRID 1755446 reaction equation
[CH:1]([C:3]1[S:7][C:6]([NH:8][C@@H:9]([CH:13]([CH3:15])[CH3:14])[C:10]([OH:12])=O)=[N:5][CH:4]=1)=[O:2].[NH2:16][C@H:17]([C:19]([NH:21][C@H:22]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH3:23])=[O:20])[CH3:18].Cl.C(Cl)CCl.ON1C2N=CC=CC=2N=N1.CN1CCOCC1>C(Cl)Cl>[CH:1]([C:3]1[S:7][C:6]([NH:8][CH:9]([CH:13]([CH3:15])[CH3:14])[C:10]([NH:16][C@@H:17]([CH3:18])[C:19]([NH:21][C@@H:22]([CH3:23])[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[O:20])=[O:12])=[N:5][CH:4]=1)=[O:2]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 15600049tert-butyl (2S)-2-[(2S)-2-aminopropanamido]propanoate hydrochlorideHCID 89858211(S)-2-(5-Formylthiazol-2-ylamino)-3-methylbutanoic acid

Product 1

HCID 89867008(2S)-tert-Butyl 2-((2S)-2-(2-(5-formylthiazol-2-ylamino)-3-methylbutanamido)propanamido)propanoateYield 42.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a material from Example 20 (560 mg, 1.227 mmol), H-Ala-Ala-OtBu.HCl (300 mg, 1.187 mmol), EDC (341 mg, 1.780 mmol), and 1-hydroxy-7-azabenzotriazole (97 mg, 0.712 mmol) in CH2Cl2 (12 mL) is added N-methylmorpholine (0.783 mL, 7.12 mmol) and the resulting solution is allowed to stir at room temp for 18 h. The solvent is removed in vacuo and the residue is purified by BIOTAGE® Silica gel chromatography on a 25 g Thompson Single Step silica cartridge using a linear gradient from 100% CH2Cl2 to 100% EtOAc over 12 column volumes to give 213 mg (42.1%) of the title compound as an off-white solid. LC/MS (Condition A): ret. T=3.17 min, (M+H)+ 427.22.

Workup

  1. customThe solvent is removed in vacuo
  2. customthe residue is purified by BIOTAGE® Silica gel chromatography on a 25 g Thompson Single Step silica cartridge

Sources & evidence

ORD record
ord-d1cebe76da0a45849d6ce4036c6dde7a
Source dataset
uspto-grants-2015_10
Patent number
US09169295B2

Reaction notes

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