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

HRID 1755439Notes

Reaction equation

HRID 1755439 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].ON1C2N=CC=CC=2N=N1.[NH2:23][C@@H:24]([CH3:45])[C:25]([NH:27][C@@H:28]([CH3:44])[C:29]([NH:31][C@@H:32]([CH2:36][C:37]1[CH:42]=[CH:41][C:40]([OH:43])=[CH:39][CH:38]=1)[C:33]([NH2:35])=[O:34])=[O:30])=[O:26].CN1CCOCC1.C(Cl)CCl>CN(C=O)C.CO>[NH2:35][C:33](=[O:34])[C@@H:32]([NH:31][C:29](=[O:30])[C@@H:28]([NH:27][C:25](=[O:26])[C@@H:24]([NH:23][C:10](=[O:12])[CH2:9][NH:8][C:6]1[S:7][C:3]([CH:1]=[O:2])=[CH:4][N:5]=1)[CH3:45])[CH3:44])[CH2:36][C:37]1[CH:42]=[CH:41][C:40]([OH:43])=[CH:39][CH:38]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 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 867000852-((5-Formylthiazol-2-yl)amino)acetic acid

Product 1

HCID 86700088(S)-N-((S)-1-Amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl)-2-((S)-2-(2-(5-formylthiazol-2-ylamino)acetamido)propanamido)propanamideYield 51.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of material from Example 3 (62 mg, 0.207 mmol), 1-hydroxy-7-azabenzotriazole (7.2 mg, 0.126 mmol), and (S)-2-amino-N-((S)-1-((S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-ylamino)-1-oxopropan-2-yl)propanamide (53.8 mg, 0.167 mmol) in anhydrous DMF (2.0 mL) is added sequentially N-methylmorpholine (125 μL, 1.137 mmol) and EDC (51.8 mg, 0.270 mmol). The resulting solution is stirred at room temperature for 6 h, diluted with MeOH (8 mL) 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 11 min, ret. T=4.19-5.20 min. The fractions containing the desired product were evaporated to dryness to give 42.4 mg (34%) of the title compound as a yellow solid as a TFA salt. LC/MS (Condition A): ret. T=1.81 min, (M+H)+ 491.15.

Workup

  1. custompurified by preparative HPLC (Condition A)
  2. customover 11 min
  3. customT=4.19-5.20 min
  4. additionThe fractions containing the desired product
  5. customwere evaporated to dryness

Sources & evidence

ORD record
ord-c84c07f09cd44000a32ea57ea73ef8ca
Source dataset
uspto-grants-2015_10
Patent number
US09169295B2

Reaction notes

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