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

HRID 1779181Notes

Reaction equation

N[C@@H](CC1C=CC(OCCCC)=CC=1)C(NC)=O.N[C@@H](CC1C=CC(OCC#CC)=CC=1)C(OC)=O.[CH2:37]([O:41][C:42]1[CH:47]=[CH:46][C:45]([CH2:48][C@H:49]([NH:54][C:55]([C@@H:57](/[CH:71]=[CH:72]/[CH2:73][CH2:74][CH2:75][CH2:76][CH2:77][CH2:78][S:79]([CH2:82][CH2:83][CH2:84][CH2:85][CH2:86][CH2:87][CH3:88])(=O)=O)[C@@:58]([OH:70])([CH2:66][CH2:67][O:68][CH3:69])[C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])=[O:56])[C:50](=[O:53])[NH:51][CH3:52])=[CH:44][CH:43]=1)[CH2:38][CH2:39][CH3:40].C(OC1C=CC(C[C@H](NC([C@@H](/C=C/CCCCCCS(CCCCCCC)(=O)=O)[C@@](O)(CCOC)C(O)=O)=O)C(=O)NC)=CC=1)CCC>>[CH2:37]([O:41][C:42]1[CH:47]=[CH:46][C:45]([CH2:48][C@H:49]([NH:54][C:55]([C@@H:57](/[CH:71]=[CH:72]/[CH2:73][CH2:74][CH2:75][CH2:76][CH2:77][CH2:78][S:79][CH2:82][CH2:83][CH2:84][CH2:85][CH2:86][CH2:87][CH3:88])[C@@:58]([OH:70])([CH2:66][CH2:67][O:68][CH3:69])[C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])=[O:56])[C:50](=[O:53])[NH:51][CH3:52])=[CH:44][CH:43]=1)[CH2:38][CH2:39][CH3:40]

Participants

Reactant 4

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

HCID 90060152(E)-(2S,3S)-3-[(S)-2-(4-butoxy-phenyl)-1-methylcarbamoyl-ethylcarbamoyl]-11-(heptane-1-sulfonyl)-2-hydroxy-2-(2-methoxy-ethyl)-undec-4-enoic acid

HCID 90060342(S)-2-amino-3-(4-butoxy-phenyl)-N-methyl-propionamide

HCID 131734854tert-butyl (E)-(2S,3S)-3-[(S)-2-(4-butoxy-phenyl)-1-methylcarbamoyl-ethylcarbamoyl]-11-(heptane-1-sulfonyl)-2-hydroxy-2-(2-methoxy-ethyl)-undec-4-enoate

Product 1

HCID 131734853tert-Butyl (E)-(2S,3S)-3-[(S)-2-(4-butoxy-phenyl)-1-methylcarbamoyl-ethylcarbamoyl]-11-heptylsulfanyl-2-hydroxy-2-(2-methoxy-ethyl)-undec-4-enoate

Procedure

tert-Butyl (E)-(2S,3S)-3-[(S)-2-(4-butoxy-phenyl)-1-methylcarbamoyl-ethylcarbamoyl]-11-heptylsulfanyl-2-hydroxy-2-(2-methoxy-ethyl)-undec-4-enoate (ESI (LC/MS positive mode) m/z 721 (M+H); Rt 2.85 min.) was synthesized by using (S)-2-amino-3-(4-butoxy-phenyl)-N-methyl-propionamide and conditions at 50° C., for 2.5 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-(4-butoxy-phenyl)-1-methylcarbamoyl-ethylcarbamoyl]-11-(heptane-1-sulfonyl)-2-hydroxy-2-(2-methoxy-ethyl)-undec-4-enoate was first synthesized (ESI (LC/MS positive mode) m/z 753 (M+H); Rt 2.17 min.) under conditions similar to those in Step C-7. Subsequently, (E)-(2S,3S)-3-[(S)-2-(4-butoxy-phenyl)-1-methylcarbamoyl-ethylcarbamoyl]-11-(heptane-1-sulfonyl)-2-hydroxy-2-(2-methoxy-ethyl)-undec-4-enoic acid (No. 5514408) was synthesized by the reaction under conditions similar to those in Step C-8.

Workup

customat 50° C.
custom5514408) was synthesized by the reaction under conditions similar to those in Step C-8

Sources & evidence

ORD record: ord-70d79cf52e5544e29e02919e6e888b2d
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09266853B2

Reaction notes

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