Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → Methyl [(1S)-2-methyl-1-({(2S)-2-[4-(4'-{2-[(3S)-2-((2S)-3-methyl-2-{[(methyloxy)carbonyl]amino}butanoyl)-6,10-dioxa-2-azaspiro[4.5]dec-3-yl]-1H-imidazol-4-yl]-4-biphenylyl)-1H-imidazol-2-yl]-1-pyrrolidinyl}carbonyl)propyl]carbamate

HRID 1748854Notes

Reaction equation

HRID 1748854 reaction equation
[CH2:1]1[C:5]2([O:10][CH2:9][CH2:8][CH2:7][O:6]2)[CH2:4][C@@H:3]([C:11]2[NH:12][CH:13]=[C:14]([C:16]3[CH:21]=[CH:20][C:19]([C:22]4[CH:27]=[CH:26][C:25]([C:28]5[N:29]=[C:30]([C@@H:33]6[CH2:37][CH2:36][CH2:35][N:34]6[C:38]([C@@H:40]([NH:44][C:45](=[O:48])[O:46][CH3:47])[CH:41]([CH3:43])[CH3:42])=[O:39])[NH:31][CH:32]=5)=[CH:24][CH:23]=4)=[CH:18][CH:17]=3)[N:15]=2)[NH:2]1.[CH3:49][O:50][C:51]([NH:53][C@H:54]([C:58](O)=[O:59])[CH:55]([CH3:57])[CH3:56])=[O:52].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>>[CH3:42][CH:41]([CH3:43])[C@H:40]([NH:44][C:45](=[O:48])[O:46][CH3:47])[C:38]([N:34]1[CH2:35][CH2:36][CH2:37][C@H:33]1[C:30]1[NH:31][CH:32]=[C:28]([C:25]2[CH:26]=[CH:27][C:22]([C:19]3[CH:18]=[CH:17][C:16]([C:14]4[N:15]=[C:11]([C@@H:3]5[CH2:4][C:5]6([O:10][CH2:9][CH2:8][CH2:7][O:6]6)[CH2:1][N:2]5[C:58](=[O:59])[C@@H:54]([NH:53][C:51]([O:50][CH3:49])=[O:52])[CH:55]([CH3:57])[CH3:56])[NH:12][CH:13]=4)=[CH:21][CH:20]=3)=[CH:23][CH:24]=2)[N:29]=1)=[O:39]

Participants

4

Reactant 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidHCID 178502363HCID 178502363, compound2×

Product 1

HCID 178502360Methyl [(1S)-2-methyl-1-({(2S)-2-[4-(4'-{2-[(3S)-2-((2S)-3-methyl-2-{[(methyloxy)carbonyl]amino}butanoyl)-6,10-dioxa-2-azaspiro[4.5]dec-3-yl]-1H-imidazol-4-yl]-4-biphenylyl)-1H-imidazol-2-yl]-1-pyrrolidinyl}carbonyl)propyl]carbamateYield 55.8%

Procedure

Methyl [(1S)-2-methyl-1-({(2S)-2-[4-(4′-{2-[(3S)-2-((2S)-3-methyl-2-{[(methyloxy)carbonyl]amino}butanoyl)-6,10-dioxa-2-azaspiro[4.5]dec-3-yl]-1H-imidazol-4-yl}-4-biphenylyl)-1H-imidazol-2-yl]-1-pyrrolidinyl}carbonyl)propyl]carbamate (47 mg, yield: 53%) was prepared from methyl [(1S)-1-({(2S)-2-[4-(4′-{2-[(3S)-6,10-dioxa-2-azaspiro[4.5]dec-3-yl]-1H-imidazol-4-yl}-4-biphenylyl)-1H-imidazol-2-yl]-1-pyrrolidinyl}carbonyl)-2-methylpropyl]carbamate (Intermediate 19) (68 mg, 0.104 mmol), N-[(methyloxy)carbonyl]-L-valine (18.2 mg, 0.104) and HATU (40 mg, 0.104 mmol), following the similar procedure outlined in Example 5. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 10.20-11.06 (m, 2H) 7.35-8.02 (m, 8H) 7.22 (d, J=7.78 Hz, 2H) 4.97-5.89 (m, 4H) 3.22-4.58 (m, 15H) 2.83-3.20 (m, 1H) 2.58-2.83 (m, 1H) 2.29-2.58 (m, 1H) 1.57-2.31 (m, 8H) 0.64-1.22 (m, 12H). HRMS: (M+H)+ calcd: 811.4143. found: 811.4142.

Sources & evidence

ORD record
ord-65417001eb024a639c6860ce8ea7d47e
Source dataset
uspto-grants-2015_10
Patent number
US09150587B2

Reaction notes

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