1,2-Dichloroethane → HCID 58813159, compound

HRID 1391721Notes

Reaction equation

HRID 1391721 reaction equation
[CH2:1]([O:4][C@H:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][CH3:15])=[CH:11][CH:12]=2)[C@@H:7]([NH:16][CH2:17][C@@H:18]([OH:30])[C@@H:19]([NH2:29])[CH2:20][C:21]2[CH:26]=[C:25](F)[CH:24]=[C:23](F)[CH:22]=2)[CH2:6]1)[CH:2]=[CH2:3].[CH2:31]([C@H:35]1[CH2:39][CH2:38][N:37]([C@@H:40]([CH2:44][CH:45]=[CH2:46])[C:41](O)=[O:42])[C:36]1=[O:47])[CH:32]([CH3:34])[CH3:33].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:1]([O:4][C@H:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][CH3:15])=[CH:11][CH:12]=2)[C@@H:7]([NH:16][CH2:17][C@@H:18]([OH:30])[C@@H:19]([NH:29][C:41](=[O:42])[C@@H:40]([N:37]2[CH2:38][CH2:39][C@H:35]([CH2:31][CH:32]([CH3:34])[CH3:33])[C:36]2=[O:47])[CH2:44][CH:45]=[CH2:46])[CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:6]1)[CH:2]=[CH2:3]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 58813136(S)-2-((S)-3-isobutyl-2-oxopyrrolidin-1-yl)pent-4-enoic acidHCID 59676141HCID 59676141, compound

Product 1

HCID 58813159HCID 58813159, compoundYield 89.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Step O (1): (2R,3S)-1-((1S,3R)-3-(Allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-3-amino-4-(3,5-difluorophenyl)butan-2-ol (20 mg, 52.3 μmol) from step E (2), (S)-2-((S)-3-isobutyl-2-oxopyrrolidin-1-yl)pent-4-enoic acid (12.5 mg, 52.3 μmol) from step M (5), EDC (10 mg, 52.3 μmol), HOBt (7.1 mg, 52.3 μmol), DIEA (46.7 μL, 262 μmol) were mixed in 1 mL of DMF. The mixture was stirred at RT for 24 h. Purified with reverse phase Prep-HPLC to give 28.2 mg of (S)—N-((2S,3R)-4-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-3-hydroxy-1-phenylbutan-2-yl)-2-((S)-3-isobutyl-2-oxopyrrolidin-1-yl)pent-4-enamide as the TFA salt: LC-MS (M+H)+=603.3 HRMS (M+H)+=604.3755 1H NMR (500 MHz, CDCl3) 8 ppm 0.80-0.96 (m, 6H) 1.08 (dd, J=10.53, 8.70 Hz, 1H) 1.23-1.38 (m, 1H) 1.54-1.66 (m, 2H) 1.96-2.06 (m, 1H) 2.26-2.45 (m, 3H) 2.51-2.77 (m, 3H) 2.85-2.95 (m, 1H) 3.03-3.16 (m, 2H) 3.28 (d, J=11.90 Hz, 1H) 3.76-3.84 (m, 3H) 3.92 (d, J=1.83 Hz, 1H) 4.03-4.12 (m, 2H) 4.20-4.29 (m, 1H) 4.46 (dd, J=10.22, 5.34 Hz, 1H) 4.73 (d, J=6.41 Hz, 1H) 4.78-4.87 (m, 1H) 4.95-5.07 (m, 2H) 5.21 (d, J=10.38 Hz, 1H) 5.30 (dd, J=17.40, 1.53 Hz, 1H) 5.54 (dd, J=14.80, 7.78 Hz, 1H) 5.84-5.98 (m, 1H) 6.71 (s, 1H) 6.95 (dd, J=8.24, 2.14 Hz, 1H) 7.11-7.28 (m, 6H) 7.34 (d, J=8.24 Hz, 1H).

Workup

  1. customPurified with reverse phase Prep-HPLC

Sources & evidence

ORD record
ord-4e0ed7f1426b46289523c036c916809f
Source dataset
uspto-grants-2008_03
Patent number
US07338974B2

Reaction notes

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