Hydrochloric Acid → (S)-2-((S)-8-(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)-1,4-dioxa-7-azaspiro[4.4]nonan-7-yl)-2-oxo-1-(tetrahydro-2H-pyran-4-yl)ethylcarbamic acid methyl ester

HRID 1751550Notes

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:122])[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[CH2:96][C:91]6([O:95][CH2:94][CH2:93][O:92]6)[CH2:90][N:89]5[C:97](=[O:110])[C@@H:98]([NH:105][C:106](=[O:109])[O:107][CH3:108])[CH:99]5[CH2:104][CH2:103][O:102][CH2:101][CH2:100]5)[NH:85][C:84]=4[CH:111]=3)[CH:76]=[CH:75][C:74]=2[C:73]2[C:68]1=[CH:69][C:70]([C:112]1[NH:116][C:115]([C@@H:117]3[CH2:121][CH2:120][CH2:119][NH:118]3)=[N:114][CH:113]=1)=[CH:71][CH:72]=2.Cl>>[CH3:108][O:107][C:106](=[O:109])[NH:105][C@@H:98]([CH:99]1[CH2:104][CH2:103][O:102][CH2:101][CH2:100]1)[C:97]([N:89]1[C@H:88]([C:86]2[NH:85][C:84]3[CH:111]=[C:80]([C:77]4[CH:76]=[CH:75][C:74]5[C:73]6[C:68](=[CH:69][C:70]([C:112]7[NH:116][C:115]([C@@H:117]8[CH2:121][CH2:120][CH2:119][N:118]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:114][CH:113]=7)=[CH:71][CH:72]=6)[C:67]([F:66])([F:122])[C:79]=5[CH:78]=4)[CH:81]=[CH:82][C:83]=3[N:87]=2)[CH2:96][C:91]2([O:95][CH2:94][CH2:93][O:92]2)[CH2:90]1)=[O:110]

Participants

Reactant 3

HCID 313Hydrochloric Acid

HCID 69675210HCID 69675210, compound

HCID 86708770methyl (S)-2-((S)-8-(6-(9,9-difluoro-7-(2-((S)-pyrrolidin-2-yl)-1H-imidazol-5-yl)-9H-fluoren-2-yl)-1H-benzo[d]imidazol-2-yl)-1,4-dioxa-7-azaspiro[4.4]nonan-7-yl)-2-oxo-1-(tetrahydro-2H-pyran-4-yl)ethylcarbamate

Product 1

HCID 86708769(S)-2-((S)-8-(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)-1,4-dioxa-7-azaspiro[4.4]nonan-7-yl)-2-oxo-1-(tetrahydro-2H-pyran-4-yl)ethylcarbamic acid methyl ester

Procedure

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-((S)-8-(6-(9,9-difluoro-7-(2-((S)-pyrrolidin-2-yl)-1H-imidazol-5-yl)-9H-fluoren-2-yl)-1H-benzo[d]imidazol-2-yl)-1,4-dioxa-7-azaspiro[4.4]nonan-7-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 972.54 [M+H]+. (30 mg, 43%).

Sources & evidence

ORD record: ord-3b60162b0ca54d1c9a19337034fc4d2b
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09156823B2

Reaction notes

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