methyl (S)-2-amino-3-(4-but-2-ynyloxy-phenyl)-propionate → tert-Butyl (E)-(2S,3S)-3-[(S)-2-(2'-fluoro-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-11-heptylsulfanyl-2-hydroxy-2-(2-methoxy-ethyl)-undec-4-enoate

HRID 1779183Notes

Reaction equation

N[C@@H](CC1C=CC(C2C=CC=CC=2F)=CC=1)C(OC)=O.N[C@@H](CC1C=CC(OCC#CC)=CC=1)C(OC)=O.[F:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=1[C:46]1[CH:51]=[CH:50][C:49]([CH2:52][C@H:53]([NH:58][C:59]([C@@H:61](/[CH:75]=[CH:76]/[CH2:77][CH2:78][CH2:79][CH2:80][CH2:81][CH2:82][S:83]([CH2:86][CH2:87][CH2:88][CH2:89][CH2:90][CH2:91][CH3:92])(=O)=O)[C@@:62]([OH:74])([CH2:70][CH2:71][O:72][CH3:73])[C:63]([O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[O:64])=[O:60])[C:54]([O:56][CH3:57])=[O:55])=[CH:48][CH:47]=1.FC1C=CC=CC=1C1C=CC(C[C@H](NC([C@@H](/C=C/CCCCCCS(CCCCCCC)(=O)=O)[C@@](O)(CCOC)C(O)=O)=O)C(OC)=O)=CC=1>>[F:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=1[C:46]1[CH:51]=[CH:50][C:49]([CH2:52][C@H:53]([NH:58][C:59]([C@@H:61](/[CH:75]=[CH:76]/[CH2:77][CH2:78][CH2:79][CH2:80][CH2:81][CH2:82][S:83][CH2:86][CH2:87][CH2:88][CH2:89][CH2:90][CH2:91][CH3:92])[C@@:62]([OH:74])([CH2:70][CH2:71][O:72][CH3:73])[C:63]([O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[O:64])=[O:60])[C:54]([O:56][CH3:57])=[O:55])=[CH:48][CH:47]=1

Participants

Reactant 4

HCID 58239373methyl (S)-2-amino-3-(4-but-2-ynyloxy-phenyl)-propionate

HCID 90060283(E)-(2S,3S)-3-[(S)-2-(2'-fluoro-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-11-(heptane-1-sulfonyl)-2-hydroxy-2-(2-methoxy-ethyl)-undec-4-enoic acid

HCID 131734856methyl (S)-2-amino-3-(2'-fluoro-biphenyl-4-yl)-propionate

HCID 131734857tert-butyl (E)-(2S,3S)-3-[(S)-2-(2'-fluoro-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-11-(heptane-1-sulfonyl)-2-hydroxy-2-(2-methoxy-ethyl)-undec-4-enoate

Product 1

HCID 131734855tert-Butyl (E)-(2S,3S)-3-[(S)-2-(2'-fluoro-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-11-heptylsulfanyl-2-hydroxy-2-(2-methoxy-ethyl)-undec-4-enoate

Procedure

tert-Butyl (E)-(2S,3S)-3-[(S)-2-(2′-fluoro-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-11-heptylsulfanyl-2-hydroxy-2-(2-methoxy-ethyl)-undec-4-enoate (ESI (LC/MS positive mode) m/z 744 (M+H); Rt 3.77 min.) was synthesized by using methyl (S)-2-amino-3-(2′-fluoro-biphenyl-4-yl)-propionate and conditions at 50° C., for 1.5 days instead of methyl (S)-2-amino-3-(4-but-2-ynyloxy-phenyl)-propionate and the conditions in Step C-6. Then, tert-butyl (E)-(2S,3S)-3-[(S)-2-(2′-fluoro-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-11-(heptane-1-sulfonyl)-2-hydroxy-2-(2-methoxy-ethyl)-undec-4-enoate was first synthesized (ESI (LC/MS positive mode) m/z 776 (M+H); Rt 2.23 min.) under conditions similar to those in Step C-7. Subsequently, (E)-(2S,3S)-3-[(S)-2-(2′-fluoro-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-11-(heptane-1-sulfonyl)-2-hydroxy-2-(2-methoxy-ethyl)-undec-4-enoic acid (No. 5540578) was synthesized by the reaction under conditions similar to those in Step C-8.

Workup

customat 50° C.
custom5540578) was synthesized by the reaction under conditions similar to those in Step C-8

Sources & evidence

ORD record: ord-a1947124accc4ebeb15d911299bb6041
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09266853B2

Reaction notes

Loading…