(3S)-2-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-7-[(3R,5S)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-5-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]carbamoyl]pyrrolidin-3-yl]-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]-3,4-dihydro-1H-isoquinoline-3-carboxamide → (S)-2-tert-Butyl 3-methyl 7-((S)-1-(tert-butoxycarbonyl)-5-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-2,5-dihydro-1H-pyrrol-3-yl)-3,4-dihydroisoquinoline-2,3(1H)-dicarboxylate

HRID 339262Notes

Reaction equation

CC(C)(C)[C@H](NC(=O)[C@@H](NC)C)C(N1[C@H](C(N[C@H]2C3C(=CC=CC=3)CCC2)=O)CC2C(=CC([C@H]3C[C@@H](C(=O)N[C@H]4C5C(=CC=CC=5)CCC4)N(C(=O)[C@@H](NC(=O)[C@@H](NC)C)C(C)(C)C)C3)=CC=2)C1)=O.[C@H:70]1([NH:80][C:81]([C@@H:83]2[CH:87]=[C:86](OS(C(F)(F)F)(=O)=O)[CH2:85][N:84]2[C:96]([O:98][C:99]([CH3:102])([CH3:101])[CH3:100])=[O:97])=[O:82])[C:79]2[C:74](=[CH:75][CH:76]=[CH:77][CH:78]=2)[CH2:73][CH2:72][CH2:71]1.CC1(C)C(C)(C)OB([C:111]2[CH:120]=[C:119]3[C:114]([CH2:115][C@@H:116]([C:128]([O:130][CH3:131])=[O:129])[N:117]([C:121]([O:123][C:124]([CH3:127])([CH3:126])[CH3:125])=[O:122])[CH2:118]3)=[CH:113][CH:112]=2)O1>>[C:99]([O:98][C:96]([N:84]1[C@H:83]([C:81](=[O:82])[NH:80][C@H:70]2[C:79]3[C:74](=[CH:75][CH:76]=[CH:77][CH:78]=3)[CH2:73][CH2:72][CH2:71]2)[CH:87]=[C:86]([C:111]2[CH:120]=[C:119]3[C:114]([CH2:115][C@@H:116]([C:128]([O:130][CH3:131])=[O:129])[N:117]([C:121]([O:123][C:124]([CH3:127])([CH3:126])[CH3:125])=[O:122])[CH2:118]3)=[CH:113][CH:112]=2)[CH2:85]1)=[O:97])([CH3:102])([CH3:100])[CH3:101]

Participants

Reactant 3

HCID 72704974(3S)-2-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-7-[(3R,5S)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-5-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]carbamoyl]pyrrolidin-3-yl]-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]-3,4-dihydro-1H-isoquinoline-3-carboxamide

HCID 86705901(S)-tert-Butyl 2-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-4-(((trifluoromethyl)sulfonyl)oxy)-2,5-dihydro-1H-pyrrole-1-carboxylate

HCID 86705903(S)-2-tert-butyl 3-methyl 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinoline-2,3(1H)-dicarboxylate

Product 1

HCID 86705902(S)-2-tert-Butyl 3-methyl 7-((S)-1-(tert-butoxycarbonyl)-5-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-2,5-dihydro-1H-pyrrol-3-yl)-3,4-dihydroisoquinoline-2,3(1H)-dicarboxylateYield 83.1%

Procedure

Following a procedure analogous to that for the synthesis of Compound D of Example 22, (S)-tert-butyl 2-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-4-(((trifluoromethyl)sulfonyl)oxy)-2,5-dihydro-1H-pyrrole-1-carboxylate (683 mg, 1.39 mmol) and (S)-2-tert-butyl 3-methyl 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinoline-2,3(1H)-dicarboxylate (726 mg, 1.74 mmol) were converted to the title compound (730 mg, 83%). MS (ESI+) m/z 632.5 (M+H)+.

Sources & evidence

ORD record: ord-ae36e0febc024a6b8e7543ed356887ce
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889712B2

Reaction notes

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