(3-{(R)-1-[5'-chloro-3,3'-difluoro-2'-(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-yl]-ethylcarbamoyl}-oxetan-3-yl)-carbamic acid 9H-fluoren-9-ylmethyl ester → 3-Amino-oxetane-3-carboxylic acid {(R)-1-[5'-chloro-3,3'-difluoro-2'-(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-yl]-ethyl}-amide

HRID 1404548Notes

Reaction equation

HRID 1404548 reaction equation
C(OC(=O)N[C@@H](C1C=CC(C2C=C(Cl)C=C(F)C=2C2N=C(C)ON=2)=CC=1F)C)(C)(C)C.BrC1C=C(Cl)C=C(F)C=1C1N=C(C)ON=1.ClC1C=C(F)C(C2N=C(C)ON=2)=C(C2C=CC([C@H](N)C)=C(F)C=2)C=1.C1C2C(COC(=O)[NH:87][C:88]3([C:92](=[O:117])[NH:93][C@@H:94]([C:96]4[CH:101]=[CH:100][C:99]([C:102]5[CH:107]=[C:106]([Cl:108])[CH:105]=[C:104]([F:109])[C:103]=5[C:110]5[N:114]=[C:113]([CH3:115])[O:112][N:111]=5)=[CH:98][C:97]=4[F:116])[CH3:95])[CH2:91][O:90][CH2:89]3)C3C(=CC=CC=3)C=2C=CC=1>>[Cl:108][C:106]1[CH:105]=[C:104]([F:109])[C:103]([C:110]2[N:114]=[C:113]([CH3:115])[O:112][N:111]=2)=[C:102]([C:99]2[CH:100]=[CH:101][C:96]([C@H:94]([NH:93][C:92]([C:88]3([NH2:87])[CH2:91][O:90][CH2:89]3)=[O:117])[CH3:95])=[C:97]([F:116])[CH:98]=2)[CH:107]=1

Participants

5

Reactant 4

HCID 67979257(3-{(R)-1-[5'-chloro-3,3'-difluoro-2'-(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-yl]-ethylcarbamoyl}-oxetan-3-yl)-carbamic acid 9H-fluoren-9-ylmethyl esterHCID 67979272(R)-1-[5'-chloro-3,3'-difluoro-2'-(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-yl]-ethylamineHCID 67979275{(R)-1-[5'-chloro-3,3'-difluoro-2'-(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-yl]ethyl}-carbamic acid tert-butyl esterHCID 684506413-(2-Bromo-4-chloro-6-fluorophenyl)-5-methyl-1,2,4-oxadiazole2×

Product 1

HCID 679792303-Amino-oxetane-3-carboxylic acid {(R)-1-[5'-chloro-3,3'-difluoro-2'-(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-yl]-ethyl}-amide

Procedure

The title compound was prepared in analogy to intermediate 5 synthesizing {(R)-1-[5′-chloro-3,3′-difluoro-2′-(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-yl]ethyl}-carbamic acid tert-butyl ester in step A (using 3-(2-bromo-4-chloro-6-fluoro-phenyl)-5-methyl-[1,2,4]oxadiazole (intermediate 10) instead of 5-(2-bromo-4-chloro-6-fluorophenyl)-2-methyl-2H-tetrazole), (R)-1-[5′-chloro-3,3′-difluoro-2′-(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-yl]-ethylamine in step B and (3-{(R)-1-[5′-chloro-3,3′-difluoro-2′-(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-yl]-ethylcarbamoyl}-oxetan-3-yl)-carbamic acid 9H-fluoren-9-ylmethyl ester in step C. White foam. MS: 449.1; [M+H]+.

Sources & evidence

ORD record
ord-9e0d85732a08417080e33ac72639c320
Source dataset
uspto-grants-2014_12
Patent number
US08912221B2

Reaction notes

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