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

HRID 1755437Notes

Reaction equation

HRID 1755437 reaction equation
[CH:1]([C:3]1[S:7][C:6]([NH:8][CH2:9][C:10]([OH:12])=O)=[N:5][CH:4]=1)=[O:2].[NH2:13][C@@H:14]([CH3:30])[C:15]([NH:17][C@@H:18]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=1)[C:19]([NH2:21])=[O:20])=[O:16].C(Cl)CCl.ON1C2N=CC=CC=2N=N1.CN1CCOCC1>CN(C=O)C>[NH2:21][C:19](=[O:20])[C@@H:18]([NH:17][C:15](=[O:16])[C@@H:14]([NH:13][C:10](=[O:12])[CH2:9][NH:8][C:6]1[S:7][C:3]([CH:1]=[O:2])=[CH:4][N:5]=1)[CH3:30])[CH2:22][C:23]1[CH:24]=[CH:25][C:26]([OH:29])=[CH:27][CH:28]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 6992565(S)-2-amino-N-((S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl)propanamideHCID 867000852-((5-Formylthiazol-2-yl)amino)acetic acid

Product 1

HCID 86700086(S)-N-((S)-1-Amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl)-2-(2-(5-formylthiazol-2-ylamino)acetamido)propanamideYield 59.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of material from Example 3 (32.2 mg, 0.107 mmol), (S)-2-amino-N-((S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl)propanamide (42.7 mg, 0.170 mmol), EDC (31.7 mg, 0.165 mmol) and 1-hydroxy-7-azabenzotriazole (10.0 mg, 0.073 mmol) is added anhydrous DMF (1.0 mL). The reaction is flushed with N2, treated with N-methylmorpholine (59 μl, 0.537 mmol), flushed with N2 and allowed to stir at room temp for 18 h. The reaction is diluted with DMF and purified by preparative HPLC (Condition A) using a PHENOMENEX® Luna Axia 30×100 mm S10 column from 10% Solvent B to 80% Solvent B over 12 min, ret. T=5.2 min. The product fractions are evaporated to dryness in a speed-vac for 18 h to give 26.7 mg (46.7%) of the title compound as a yellow solid as a TFA salt. LC/MS (Condition A): ret. T=1.65 min, (M+H)+ 420.09.

Workup

  1. customThe reaction is flushed with N2
  2. customflushed with N2
  3. additionThe reaction is diluted with DMF
  4. custompurified by preparative HPLC (Condition A)
  5. customover 12 min
  6. customT=5.2 min
  7. customThe product fractions are evaporated to dryness in a speed-vac for 18 h

Sources & evidence

ORD record
ord-115a2b2c595a4926848f5568f7b5e855
Source dataset
uspto-grants-2015_10
Patent number
US09169295B2

Reaction notes

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