1,2-Dichloroethane → N-((S)-1-((S)-1-((S)-1-Amino-3-(4-hydroxyphenyl)-1-oxopropan-2-ylamino)-1-oxopropan-2-ylamino)-1-oxopropan-2-yl)-2-(5-formylthiazol-2-ylamino)-3-methylbutanamide

HRID 1755443Notes

Reaction equation

HRID 1755443 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]([CH3:38])[C:18]([NH:20][C@@H:21]([CH3:37])[C:22]([NH:24][C@@H:25]([CH2:29][C:30]1[CH:35]=[CH:34][C:33]([OH:36])=[CH:32][CH:31]=1)[C:26]([NH2:28])=[O:27])=[O:23])=[O:19].C(Cl)CCl.ON1C2N=CC=CC=2N=N1.CN1CCOCC1.C(O)(C(F)(F)F)=O>CN(C=O)C>[NH2:28][C:26](=[O:27])[C@@H:25]([NH:24][C:22](=[O:23])[C@@H:21]([NH:20][C:18](=[O:19])[C@@H:17]([NH:16][C:10](=[O:12])[CH:9]([NH:8][C:6]1[S:7][C:3]([CH:1]=[O:2])=[CH:4][N:5]=1)[CH:13]([CH3:15])[CH3:14])[CH3:38])[CH3:37])[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([OH:36])=[CH:32][CH:31]=1

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 181649HOAtHCID 68279251(S)-2-amino-N-((S)-1-((S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-ylamino)-1-oxopropan-2-yl)propanamideHCID 89858211(S)-2-(5-Formylthiazol-2-ylamino)-3-methylbutanoic acid

Product 1

HCID 86700095N-((S)-1-((S)-1-((S)-1-Amino-3-(4-hydroxyphenyl)-1-oxopropan-2-ylamino)-1-oxopropan-2-ylamino)-1-oxopropan-2-yl)-2-(5-formylthiazol-2-ylamino)-3-methylbutanamideYield 74.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Following the procedure described in Example 4, except using the material from Example 20 (77 mg, 0.169 mmol), (S)-2-amino-N-((S)-1-((S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-ylamino)-1-oxopropan-2-yl)propanamide (61.2 mg, 0.19 mmol), EDC (56.2 mg, 0.293 mmol), 1-hydroxy-7-azabenzotriazole (19.2 mg, 0.141 mmol), anhydrous DMF (2 mL) and N-methylmorpholine (104 μL, 0.946 mmol), 67 mg (54.5%) of the title compound is obtained as a yellow solid as a TFA salt. Purification is done by preparative HPLC (Condition A) using a PHENOMENEX® Luna Axia 30×100 mm S10 column from 15% Solvent B to 90% Solvent B over 1 min, ret. T=6.98 min.

Sources & evidence

ORD record
ord-d65f75c74b9f4f668a225bb03bfe011b
Source dataset
uspto-grants-2015_10
Patent number
US09169295B2

Reaction notes

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