Dichloromethane → 2,4,7,12-Tetraazatridecan-13-oic acid, 10-hydroxy-2,5-dimethyl-1-(2-(1-methylethyl)-4-oxazolyl)-3,6-dioxo-8,11-bis(phenylmethyl)-, 5-isoxazolylmethyl ester, (5S-(5R*,8R*,10R*,11R*))-

HRID 433789Notes

Reaction equation

HRID 433789 reaction equation
[CH3:1][N:2]([C:12]([NH:14][C@H:15]([C:17]([OH:19])=O)[CH3:16])=[O:13])[CH2:3][C:4]1[N:5]=[C:6]([CH:9]([CH3:11])[CH3:10])[O:7][CH:8]=1.NC(CC1C=CC=CC=1)CC(O)C(NC(OCC1SC=NC=1)=O)CC1C=CC=CC=1.[NH2:50][C@@H:51]([CH2:73][C:74]1[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=1)[CH2:52][C@H:53]([OH:72])[C@@H:54]([NH:62][C:63]([O:65][CH2:66][C:67]1[O:71][N:70]=[CH:69][CH:68]=1)=[O:64])[CH2:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1.C(Cl)Cl>CO>[CH3:1][N:2]([C:12]([NH:14][C@H:15]([C:17]([NH:50][C@@H:51]([CH2:73][C:74]1[CH:75]=[CH:76][CH:77]=[CH:78][CH:79]=1)[CH2:52][C@H:53]([OH:72])[C@@H:54]([NH:62][C:63]([O:65][CH2:66][C:67]1[O:71][N:70]=[CH:69][CH:68]=1)=[O:64])[CH2:55][C:56]1[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=1)=[O:19])[CH3:16])=[O:13])[CH2:3][C:4]1[N:5]=[C:6]([CH:9]([CH3:10])[CH3:11])[O:7][CH:8]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 98453355-amino-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexaneHCID 10563897N-((N-methyl-N-((2-isopropyl-4-oxazolyl)methyl)amino)carbonyl)-L-alanineHCID 57164722(2S,3S,5S)-5-amino-2-(N-((5-isoxazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane

Product 1

HCID 4829592,4,7,12-Tetraazatridecan-13-oic acid, 10-hydroxy-2,5-dimethyl-1-(2-(1-methylethyl)-4-oxazolyl)-3,6-dioxo-8,11-bis(phenylmethyl)-, 5-isoxazolylmethyl ester, (5S-(5R*,8R*,10R*,11R*))-Yield 64%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Using the procedure of Example 1U but replacing N-((N-methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)carbonyl)-L-valine with N-((N-methyl-N-((2-isopropyl-4-oxazolyl)methyl)amino)carbonyl)-L-alanine and replacing 2S,3S,5S)-5-amino-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane with (2S,3S,5S)-5-amino-2-(N-((5-isoxazolyl)methoxy-carbonyl)amino)-1,6-diphenyl-3-hydroxyhexane provided, after silica gel chromatography using 92:8 CH2Cl2:CH3OH, the desired compound (Rf 0.48, 92:8 CH2Cl2:CH3OH) in 64% yield. 1H NMR (DMSO-d6) δ 1.08 (d, 3H), 1.24 (d, 6H), 1.50 (m, 2H), 2.82 (s, 3H), 3.0 (m, 1H), 4.25 (s, 2H), 4.60 (d, 1H), 5.05 (s, 2H), 6.20 (br d, 1H), 6.32 (d, 1H), 7.20 (m, 11H), 7.50 (br d, 1H), 7.78 (s, 1H), 8.51 (d, 1H). Mass spectrum: (M+H)+=661.

Workup

  1. customprovided

Sources & evidence

ORD record
ord-494229d9929147cda697711e4f1fa1db
Source dataset
uspto-grants-2003_12
Patent number
US06667404B2

Reaction notes

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