2-(methoxycarbonylamino)-2-(tetrahydro-2H-pyran-4-yl)acetic acid → [1-(6-{5-[4-(6-{2-[1-(2-Methoxycarbonylamino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-naphthalen-2-yl)-phenyl]-1H-imidazol-2-yl}-5-aza-spiro[2.4]heptane-5-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester

HRID 1751460Notes

Reaction equation

HRID 1751460 reaction equation
[CH3:1][O:2][C:3](=[O:66])[NH:4][CH:5](C1CCOCC1)[C:6]([N:8]1[CH2:12][C:11](F)(F)[CH2:10][CH:9]1[C:15]1[NH:16][C:17]([C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:35]=[CH:34][C:33]4[C:28](=[CH:29][CH:30]=[C:31]([C:36]5[NH:37][C:38]([CH:41]6[CH2:45][CH2:44][CH2:43][N:42]6[C:46](=[O:59])[CH:47]([NH:54][C:55]([O:57][CH3:58])=[O:56])[C:48]6[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=6)=[N:39][CH:40]=5)[CH:32]=4)[CH:27]=3)=[CH:22][CH:21]=2)=[CH:18][N:19]=1)=[O:7].COC(N[CH:72]([CH:76]1CCOCC1)[C:73](O)=O)=O.[CH2:82](OC(N1C(C2NC(C3C=CC(B4OC(C)(C)C(C)(C)O4)=CC=3)=CN=2)CC2(CC2)C1)=O)[C:83]1C=CC=CC=1.C(OC(N1CC(F)(F)CC1C1NC(C2C=CC(B3OC(C)(C)C(C)(C)O3)=CC=2)=CN=1)=O)C1C=CC=CC=1>>[CH3:1][O:2][C:3](=[O:66])[NH:4][CH:5]([C:6]([N:8]1[CH:9]([C:15]2[NH:16][C:17]([C:20]3[CH:25]=[CH:24][C:23]([C:26]4[CH:35]=[CH:34][C:33]5[C:28](=[CH:29][CH:30]=[C:31]([C:36]6[NH:37][C:38]([CH:41]7[CH2:45][CH2:44][CH2:43][N:42]7[C:46](=[O:59])[CH:47]([NH:54][C:55]([O:57][CH3:58])=[O:56])[C:48]7[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=7)=[N:39][CH:40]=6)[CH:32]=5)[CH:27]=4)=[CH:22][CH:21]=3)=[CH:18][N:19]=2)[CH2:10][C:11]2([CH2:83][CH2:82]2)[CH2:12]1)=[O:7])[CH:72]([CH3:76])[CH3:73]

Participants

5

Reactant 4

HCID 585162412-(methoxycarbonylamino)-2-(tetrahydro-2H-pyran-4-yl)acetic acidHCID 69675409HCID 69675409, compoundHCID 69675444HCID 69675444, compoundHCID 86708746HCID 86708746, compound

Product 1

HCID 77335274[1-(6-{5-[4-(6-{2-[1-(2-Methoxycarbonylamino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-naphthalen-2-yl)-phenyl]-1H-imidazol-2-yl}-5-aza-spiro[2.4]heptane-5-carbonyl)-2-methyl-propyl]-carbamic acid methyl esterYield 34%

Procedure

[1-(6-{5-[4-(6-{2-[1-(2-Methoxycarbonylamino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-naphthalen-2-yl)-phenyl]-1H-imidazol-2-yl}-5-aza-spiro[2.4]heptane-5-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester (0.10 g, 34%) was prepared following the procedure for [2-(4,4-Difluoro-2-{5-[4-(6-{2-[1-(2-methoxycarbonylamino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-naphthalen-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidin-1-yl)-2-oxo-1-(tetrahydro-pyran-4-yl)-ethyl]-carbamic acid methyl ester, substituting 2-Methoxycarbonylamino-3-methyl-butyric acid for Methoxycarbonylamino-(tetrahydro-pyran-4-yl)-acetic acid and 6-{5-[4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-5-aza-spiro[2.4]heptane-5-carboxylic acid benzyl ester for 4,4-Difluoro-2-{5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid benzyl ester. LCMS-ESI+: calc'd for C49H52N8O6: 848.40 (M+); Found: 849.96 (M+H+).

Sources & evidence

ORD record
ord-1c6fc835390a4c3489e4e87147a87d02
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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