Hydrochloric Acid → (S)-2-((1R,3 S,4R)-3-(6-(9,9-difluoro-7-(2-((S)-1-((R)-2-(methoxycarbonylamino)-2-phenylacetyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-9H-fluoren-2-yl)-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptan-2-yl)-2-oxo-1-(tetrahydro-2H-pyran-4-yl)ethylcarbamic acid methyl ester

HRID 1751551Notes

Reaction equation

COC(=O)N[C@@H](C(C)C)C(N1[C@H](C2NC(C3C=CC(C4C=CC5C(=CC=C(C6NC([C@@H]7CCCN7[C:48](=[O:61])[C@H:49]([NH:56][C:57]([O:59][CH3:60])=[O:58])[C:50]7[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=7)=NC=6)C=5)C=4)=CC=3)=CN=2)CC2(OCCO2)C1)=O.[F:66][C:67]1([F:120])[C:79]2[CH:78]=[C:77]([C:80]3[CH:81]=[CH:82][C:83]4[N:87]=[C:86]([C@@H:88]5[C@H:93]6[CH2:94][C@@H:90]([CH2:91][CH2:92]6)[N:89]5[C:95](=[O:108])[C@@H:96]([NH:103][C:104](=[O:107])[O:105][CH3:106])[CH:97]5[CH2:102][CH2:101][O:100][CH2:99][CH2:98]5)[NH:85][C:84]=4[CH:109]=3)[CH:76]=[CH:75][C:74]=2[C:73]2[C:68]1=[CH:69][C:70]([C:110]1[NH:114][C:113]([C@@H:115]3[CH2:119][CH2:118][CH2:117][NH:116]3)=[N:112][CH:111]=1)=[CH:71][CH:72]=2.Cl>>[CH3:106][O:105][C:104](=[O:107])[NH:103][C@@H:96]([CH:97]1[CH2:98][CH2:99][O:100][CH2:101][CH2:102]1)[C:95]([N:89]1[C@H:88]([C:86]2[NH:85][C:84]3[CH:109]=[C:80]([C:77]4[CH:76]=[CH:75][C:74]5[C:73]6[C:68](=[CH:69][C:70]([C:110]7[NH:114][C:113]([C@@H:115]8[CH2:119][CH2:118][CH2:117][N:116]8[C:48](=[O:61])[C@H:49]([NH:56][C:57]([O:59][CH3:60])=[O:58])[C:50]8[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=8)=[N:112][CH:111]=7)=[CH:71][CH:72]=6)[C:67]([F:66])([F:120])[C:79]=5[CH:78]=4)[CH:81]=[CH:82][C:83]=3[N:87]=2)[C@H:93]2[CH2:94][C@H:90]1[CH2:91][CH2:92]2)=[O:108]

Participants

Reactant 3

HCID 313Hydrochloric Acid

HCID 69675210HCID 69675210, compound

HCID 86708772methyl (S)-2-((1R,3S,4R)-3-(6-(9,9-difluoro-7-(2-((S)-pyrrolidin-2-yl)-1H-imidazol-5-yl)-9H-fluoren-2-yl)-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptan-2-yl)-2-oxo-1-(tetrahydro-2H-pyran-4-yl)ethylcarbamate

Product 1

HCID 86708771(S)-2-((1R,3 S,4R)-3-(6-(9,9-difluoro-7-(2-((S)-1-((R)-2-(methoxycarbonylamino)-2-phenylacetyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-9H-fluoren-2-yl)-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptan-2-yl)-2-oxo-1-(tetrahydro-2H-pyran-4-yl)ethylcarbamic acid methyl ester

Procedure

The title compound was prepared according to the method employed to prepare (S)-1-((S)-8-(5-(4-(6-(2-((S)-1-((R)-2-(methoxycarbonylamino)-2-phenylacetyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)-1,4-dioxa-7-azaspiro[4.4]nonan-7-yl)-3-methyl-1-oxobutan-2-ylcarbamic acid methyl ester, except that methyl (S)-2-((1R,3S,4R)-3-(6-(9,9-difluoro-7-(2-((S)-pyrrolidin-2-yl)-1H-imidazol-5-yl)-9H-fluoren-2-yl)-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptan-2-yl)-2-oxo-1-(tetrahydro-2H-pyran-4-yl)ethylcarbamate 3× HCl salt was used instead of methyl (S)-3-methyl-1-oxo-1-((S)-8-(5-(4-(6-(2-((S)-pyrrolidin-2-yl)-1H-imidazol-5-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)-1,4-dioxa-7-azaspiro[4.4]nonan-7-yl)butan-2-ylcarbamate 3HCl salt. MS (ESI) m/z 939.91 [M+H]+. (102 mg, 57%).

Sources & evidence

ORD record: ord-a7ed8b91232c480d9044eb4729cfd5f1
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09156823B2

Reaction notes

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