Diisopropylethylamine → HCID 69020035, compound

HRID 133798Notes

Reaction equation

HRID 133798 reaction equation
[CH3:1][NH:2][C@H:3]([C:14]([NH:16][C@H:17]([C:22]([N:24]([C@@H:26]([CH:33]([CH3:35])[CH3:34])/[CH:27]=[C:28](/[C:30]([OH:32])=O)\[CH3:29])[CH3:25])=[O:23])[C:18]([CH3:21])([CH3:20])[CH3:19])=[O:15])[C:4]([CH3:13])([CH3:12])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7](C)[CH:6]=1.O[C:37]1C2N=NNC=2C=CC=1.Cl.CN(C)CCCN=C=NCC.C(N(C(C)C)CC)(C)C.[F:67][C:68]([F:73])([F:72])[C:69]([OH:71])=[O:70].[NH:74]1[CH2:95][CH2:94][CH2:93][C@H:75]1[C:76]([N:78]1[CH2:92][CH2:91][CH2:90][C@H:79]1[C:80]([NH:82][CH2:83][C:84]1[CH:89]=[CH:88][CH:87]=[CH:86][CH:85]=1)=[O:81])=[O:77]>C(#N)C>[F:67][C:68]([F:73])([F:72])[C:69]([OH:71])=[O:70].[CH3:29]/[C:28](=[CH:27]\[C@@H:26]([N:24]([CH3:25])[C:22](=[O:23])[C@H:17]([C:18]([CH3:20])([CH3:19])[CH3:21])[NH:16][C:14](=[O:15])[C@H:3]([C:4]([CH3:12])([CH3:13])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH3:37])[CH:6]=1)[NH:2][CH3:1])[CH:33]([CH3:34])[CH3:35])/[C:30]([N:74]1[CH2:95][CH2:94][CH2:93][C@@H:75]1[C:76]([N:78]1[CH2:92][CH2:91][CH2:90][C@@H:79]1[C:80]([NH:82][CH2:83][C:84]1[CH:85]=[CH:86][CH:87]=[CH:88][CH:89]=1)=[O:81])=[O:77])=[O:32]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10435564HCID 10435564, compoundHCID 69021415HCID 69021415, compoundHCID 178418300HCID 178418300, compound

Product 1

HCID 69020035HCID 69020035, compoundYield 69.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

By using an analogous procedure described in General Procedure I Method A, N,β,β,3-tetramethyl-L-phenylalanyl-N1-[(1S,2E)-3-carboxy-1-isopropyl-2-butenyl]-N1,3-dimethyl-L-valinamide (100 mg, 0.205 mmol) is treated with hydroxybenzotriazole (36 mg, 0.27 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (59 mg, 0.31 mmol) in anhydrous acetonitrile (10 ml) at room temperature for 40 hours, followed by addition of diisopropylethylamine (0.143 ml, 0.82 mmol) and a solution of L-prolyl-N-benzyl-L-prolinamide trifluoroacetic acid salt (255 mg, 0.615 mmol) in anhydrous acetonitrile (3 ml). After stirring at room temperature for 4 hours, the product is purified by preparative HPLC, to provide the trifluoroacetic acid salt of the title compound (126.6 mg, 69%) as a white amorphous solid. MS (ES): m/z 771.5 (M+H). IR cm−1: 3306.94, 2969.17, 1673.9, 1642.27, 1203.38. Analytical HPLC: (4.6×150 mm YMC Pack Pro C18 column eluted with 10 to 100% acetonitrile in water containing 0.02% formic acid over 35 minutes): 92.56% (at 17.7 minutes) of 1-{(2E,4S)-2,5-dimethyl-4-[methyl(N,β,β,3-tetramethyl-L-phenylalanyl-3-methyl-L-valyl)amino]hex-2-enoyl}-D-prolyl-N-benzyl-D-prolinamide, and 6.92% (at 18.5 minutes) of the other diastereomer.

Workup

  1. customthe product is purified by preparative HPLC

Sources & evidence

ORD record
ord-d83e1e80f30848a6a82d7893402aa35a
Source dataset
uspto-grants-2008_06
Patent number
US07390910B2

Reaction notes

Loading…