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

HRID 1755473Notes

Reaction equation

HRID 1755473 reaction equation
[CH:1]([C:3]1[S:7][C:6]([N:8]2[CH2:12][CH2:11][CH2:10][C@H:9]2[C:13]([OH:15])=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(O)(C(F)(F)F)=O.ON1C2N=CC=CC=2N=N1.C(Cl)CCl.CN1CCOCC1>CN(C=O)C.CO>[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:13]([C@@H:9]1[CH2:10][CH2:11][CH2:12][N:8]1[C:6]1[S:7][C:3]([CH:1]=[O:2])=[CH:4][N:5]=1)=[O:15])[CH3:38])[CH3:37])[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([OH:36])=[CH:32][CH:31]=1

Participants

9

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 89858146(S)-1-(5-Formylthiazol-2-yl)pyrrolidine-2-carboxylic acid

Product 1

HCID 86700119(S)-N-((S)-1-((S)-1-((S)-1-Amino-3-(4-hydroxyphenyl)-1-oxopropan-2-ylamino)-1-oxopropan-2-ylamino)-1-oxopropan-2-yl)-1-(5-formylthiazol-2-yl)pyrrolidine-2-carboxamideYield 63%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of material from Example 80 (25 mg, 0.110 mmol), (S)-2-amino-N-((S)-1-((S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-ylamino)-1-oxopropan-2-yl)propanamide, TFA (25 mg, 0.057 mmol), and 1-hydroxy-7-azabenzotriazole (4 mg, 0.029 mmol) in anhydrous DMF (2 mL) is added sequentially EDC (12 mg, 0.063 mmol), followed by N-methylmorpholine (40 μl, 0.364 mmol). The resulting solution is stirred at room temp for 45 min, diluted with MeOH (5 mL) and purified by preparative HPLC (Condition A) using a PHENOMENEX® Luna Axia 30×100 mm S10 column from 15% Solvent B to 85% Solvent B over 11 min, ret. T=5.9 min. The fractions containing the desired product were evaporated to dryness to give 23 mg (63%) of the title compound as a white solid as a TFA salt. LC/MS (Condition A): ret. T=2.04 min, (M+H)+ 531.27.

Workup

  1. custompurified by preparative HPLC (Condition A)
  2. customover 11 min
  3. customT=5.9 min
  4. additionThe fractions containing the desired product
  5. customwere evaporated to dryness

Sources & evidence

ORD record
ord-e0bc8afea58d4071b63893dc4e79fc51
Source dataset
uspto-grants-2015_10
Patent number
US09169295B2

Reaction notes

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