N-((R)-1-{5-[3,5-dichloro-2-(2,2-difluoro-ethoxy)-phenyl]-3-fluoro-pyridin-2-yl}-ethyl)-acetamide → 3-Amino-oxetane-3-carboxylic acid ((R)-1-{5-[3,5-dichloro-2-(2,2-difluoro-ethoxy)-phenyl]-3-fluoro-pyridin-2-yl}-ethyl)-amide

HRID 1404541Notes

Reaction equation

HRID 1404541 reaction equation
ClC1C(OCC(F)F)=C(C2C=C(F)C([C@H](NC(=O)C)C)=NC=2)C=C(Cl)C=1.BrC1C=C(Cl)C=C(Cl)C=1OCC(F)F.ClC1C(OCC(F)F)=C(C2C=C(F)C([C@H](N)C)=NC=2)C=C(Cl)C=1.C1C2C(COC(=O)[NH:80][C:81]3([C:85](=[O:109])[NH:86][C@@H:87]([C:89]4[C:94]([F:95])=[CH:93][C:92]([C:96]5[CH:101]=[C:100]([Cl:102])[CH:99]=[C:98]([Cl:103])[C:97]=5[O:104][CH2:105][CH:106]([F:108])[F:107])=[CH:91][N:90]=4)[CH3:88])[CH2:84][O:83][CH2:82]3)C3C(=CC=CC=3)C=2C=CC=1>>[Cl:103][C:98]1[C:97]([O:104][CH2:105][CH:106]([F:107])[F:108])=[C:96]([C:92]2[CH:93]=[C:94]([F:95])[C:89]([C@H:87]([NH:86][C:85]([C:81]3([NH2:80])[CH2:84][O:83][CH2:82]3)=[O:109])[CH3:88])=[N:90][CH:91]=2)[CH:101]=[C:100]([Cl:102])[CH:99]=1

Participants

5

Reactant 4

HCID 44196682N-((R)-1-{5-[3,5-dichloro-2-(2,2-difluoro-ethoxy)-phenyl]-3-fluoro-pyridin-2-yl}-ethyl)-acetamideHCID 441966832-[(R)-1-Aminoethyl]-3-fluoro-5-[2-(2,2-difluoroethoxy)-3,5-dichlorophenyl]pyridineHCID 441966871-Bromo-3,5-dichloro-2-(2,2-difluoroethoxy)benzene2×HCID 86667252[3-((R)-1-{5-[3,5-dichloro-2-(2,2-difluoro-ethoxy)-phenyl]-3-fluoro-pyridin-2-yl]-ethylcarbamoyl)-oxetan-3-yl}-carbamic acid 9H-fluoren-9-ylmethyl ester

Product 1

HCID 866672513-Amino-oxetane-3-carboxylic acid ((R)-1-{5-[3,5-dichloro-2-(2,2-difluoro-ethoxy)-phenyl]-3-fluoro-pyridin-2-yl}-ethyl)-amide

Procedure

The title compound was prepared in analogy to intermediate 1 synthesizing N—((R)-1-{5-[3,5-dichloro-2-(2,2-difluoro-ethoxy)-phenyl]-3-fluoro-pyridin-2-yl}-ethyl)-acetamide in step A (using 1-bromo-3,5-dichloro-2-(2,2-difluoro-ethoxy)-benzene (intermediate 9) instead of 3-(2-bromo-4-chloro-6-fluoro-phenyl)-5-methyl-[1,2,4]oxadiazole), (R)-1-{5-[3,5-dichloro-2-(2,2-difluoro-ethoxy)-phenyl]-3-fluoro-pyridin-2-yl}-ethylamine in step B and [3-((R)-1-{5-[3,5-dichloro-2-(2,2-difluoro-ethoxy)-phenyl]-3-fluoro-pyridin-2-yl}-ethylcarbamoyl)-oxetan-3-yl]-carbamic acid 9H-fluoren-9-ylmethyl ester in step C. White foam. MS: 464.1 [M+H]+.

Sources & evidence

ORD record
ord-b7849259de6c4730800ac7613e0a00e3
Source dataset
uspto-grants-2014_12
Patent number
US08912221B2

Reaction notes

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