1,2-Dichloroethane → (9H-Fluoren-9-yl)methyl(S)-1-((S)-1-((S)-1-((S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-ylamino)-1-oxopropan-2-ylamino)-1-oxopropan-2-ylamino)-3-(4-hydroxyphenyl)-1-oxopropan-2-ylcarbamate

HRID 1755463Notes

Reaction equation

HRID 1755463 reaction equation
[NH2:1][C@@H:2]([CH3:23])[C:3]([NH:5][C@@H:6]([CH3:22])[C:7]([NH:9][C@@H:10]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=1)[C:11]([NH2:13])=[O:12])=[O:8])=[O:4].[C:24]([NH:41][C@H:42]([C:51](O)=[O:52])[CH2:43][C:44]1[CH:49]=[CH:48][C:47]([OH:50])=[CH:46][CH:45]=1)([O:26][CH2:27][CH:28]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[C:34]2[C:29]1=[CH:30][CH:31]=[CH:32][CH:33]=2)=[O:25].ON1C2N=CC=CC=2N=N1.CN1CCOCC1.C(Cl)CCl>CN(C=O)C>[NH2:13][C:11](=[O:12])[C@@H:10]([NH:9][C:7](=[O:8])[C@@H:6]([NH:5][C:3](=[O:4])[C@@H:2]([NH:1][C:51](=[O:52])[C@@H:42]([NH:41][C:24](=[O:25])[O:26][CH2:27][CH:28]1[C:40]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[C:34]2[C:29]1=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH2:43][C:44]1[CH:45]=[CH:46][C:47]([OH:50])=[CH:48][CH:49]=1)[CH3:23])[CH3:22])[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 6957986(2S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(4-hydroxyphenyl)propanoic acidHCID 68279251(S)-2-amino-N-((S)-1-((S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-ylamino)-1-oxopropan-2-yl)propanamide

Product 1

HCID 89869729(9H-Fluoren-9-yl)methyl(S)-1-((S)-1-((S)-1-((S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-ylamino)-1-oxopropan-2-ylamino)-1-oxopropan-2-ylamino)-3-(4-hydroxyphenyl)-1-oxopropan-2-ylcarbamateYield 55.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Following the procedure described in Example 7, except using (S)-2-amino-N-((S)-1-((S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-ylamino)-1-oxopropan-2-yl)propanamide (40 mg, 0.124 mmol), Fmoc-L Tyrosine (52.6 mg, 0.130 mmol), 1-hydroxy-7-azabenzotriazole (9.5 mg, 0.070 mmol), anhydrous DMF (1.2 mL), N-methylmorpholine (16 μL, 0.146 mmol), EDC (28.5 mg, 0.149 mmol) and stirring at room temp for 4 h 15 min, 48.4 mg (47.5%) of the title compound is isolated as an off white solid. Purification is done by preparative HPLC (Condition A) using a PHENOMENEX® Luna Axia 30×100 mm S10 column from 35% Solvent B to 100% Solvent B over 11 min, ret. T=8.79 min. LC/MS (Condition A): ret. T=3.46 min, (M+H)+ 708.32. Analytical HPLC: (Condition A): >99%, ret. T=21.87 min, (Condition B): >99%, ret. T=22.15 min, (Condition C): >98%, ret. T=13.82 min, (Condition D): >99%, ret. T=12.79 min.

Sources & evidence

ORD record
ord-4ec81b5c7cbd40de9b345bcfd12833b0
Source dataset
uspto-grants-2015_10
Patent number
US09169295B2

Reaction notes

Loading…