HCID 178502181, compound → HCID 178502418, compound

HRID 1751481Notes

Reaction equation

HRID 1751481 reaction equation
[CH3:1][O:2][C:3](=[O:60])[NH:4][CH:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16]1[NH:17][C:18]([C:21]2[CH:30]=[CH:29][C:28]3[C:23](=[CH:24][CH:25]=[C:26]([C:31]4[CH:32]=[C:33]5[C:57](=[CH:58][CH:59]=4)[C:37]4[NH:38][C:39]([CH:41]6[CH2:45][CH2:44][CH2:43][N:42]6[C:46](=[O:56])[CH:47]([NH:51][C:52]([O:54][CH3:55])=[O:53])[CH:48]([CH3:50])[CH3:49])=[N:40][C:36]=4[CH2:35][CH2:34]5)[CH:27]=3)[CH:22]=2)=[CH:19][N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7]>C(Cl)Cl.O=[Mn]=O>[CH3:55][O:54][C:52]([NH:51][C@@H:47]([CH:48]([CH3:50])[CH3:49])[C:46]([N:42]1[CH2:43][CH2:44][CH2:45][C@H:41]1[C:39]1[NH:38][C:37]2[C:57]3[C:33]([CH:34]=[CH:35][C:36]=2[N:40]=1)=[CH:32][C:31]([C:26]1[CH:27]=[C:28]2[C:23](=[CH:24][CH:25]=1)[CH:22]=[C:21]([C:18]1[NH:17][C:16]([C@@H:12]4[CH2:13][CH2:14][CH2:15][N:11]4[C:9](=[O:10])[C@@H:5]([NH:4][C:3](=[O:60])[O:2][CH3:1])[CH:6]([CH3:8])[CH3:7])=[N:20][CH:19]=1)[CH:30]=[CH:29]2)=[CH:59][CH:58]=3)=[O:56])=[O:53]

Participants

4

Reactant 1

HCID 178502181HCID 178502181, compound

Product 1

HCID 178502418HCID 178502418, compoundYield 48.4%

Reagents, catalysts & solvents 2

HCID 14801Manganese dioxideCatalyst2×HCID 6344DichloromethaneSolvent

Procedure

To (1-{2-[5-(6-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-4,5-dihydro-1H-naphtho[1,2-d]imidazol-7-yl}-naphthalen-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (13.0 mg, 0.016 mmol) in CH2Cl2 (1 mL) was added MnO2 (2.8 mg, 0.032 mmol). The reaction was stirred overnight then additional MnO2 (1.4 mg, 0.016 mmol) was added. After stirring for 3 hours, the reaction was filtered through a Whatman 0.45 mM PTFE filter. The filtrate was concentrated then purified by preparative reverse phase HPLC (Gemini, 10 to 45% ACN/H2O+0.1% TFA) to yield methyl (S)-1-((S)-2-(5-(6-(2-((S)-1-((S)-2-methoxycarbonylamino-3-methylbutanoyl)pyrrolidin-2-yl)-1H-naphtho[1,2-d]imidazol-7-yl)naphthalen-2-yl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (6.3 mg, 48%). LCMS-ESI+: calculated for C46H53N8O6: 813.4; observed [M+1]+: 813.4.

Workup

  1. stirringAfter stirring for 3 hours
  2. filtrationthe reaction was filtered through a Whatman 0.45 mM PTFE
  3. filtrationfilter
  4. concentrationThe filtrate was concentrated
  5. customthen purified by preparative reverse phase HPLC (Gemini, 10 to 45% ACN/H2O+0.1% TFA)

Sources & evidence

ORD record
ord-ba37de62bbad4a4eafa86e1d1d487131
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

Loading…