Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → HCID 178502280, compound

HRID 1748851Notes

Reaction equation

HRID 1748851 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@H:6]([C:8]([OH:10])=O)[CH3:7])=[O:4].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:35]1[C:39]2([O:44][CH2:43][CH2:42][CH2:41][O:40]2)[CH2:38][C@@H:37]([C:45]2[NH:46][CH:47]=[C:48]([C:50]3[CH:55]=[CH:54][C:53]([C:56]4[CH:61]=[CH:60][C:59]([C:62]5[N:63]=[C:64]([C@@H:67]6[CH2:71][CH2:70][CH2:69][N:68]6[C:72]([C@@H:74]([NH:78][C:79](=[O:82])[O:80][CH3:81])[CH:75]([CH3:77])[CH3:76])=[O:73])[NH:65][CH:66]=5)=[CH:58][CH:57]=4)=[CH:52][CH:51]=3)[N:49]=2)[NH:36]1>CN(C=O)C>[CH3:7][C@H:6]([NH:5][C:3](=[O:4])[O:2][CH3:1])[C:8]([N:36]1[C@H:37]([C:45]2[NH:46][CH:47]=[C:48]([C:50]3[CH:51]=[CH:52][C:53]([C:56]4[CH:61]=[CH:60][C:59]([C:62]5[N:63]=[C:64]([C@@H:67]6[CH2:71][CH2:70][CH2:69][N:68]6[C:72](=[O:73])[C@@H:74]([NH:78][C:79]([O:80][CH3:81])=[O:82])[CH:75]([CH3:77])[CH3:76])[NH:65][CH:66]=5)=[CH:58][CH:57]=4)=[CH:54][CH:55]=3)[N:49]=2)[CH2:38][C:39]2([O:44][CH2:43][CH2:42][CH2:41][O:40]2)[CH2:35]1)=[O:10]

Participants

5

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 13048344N-carbomethoxy-L-alanineHCID 178502363HCID 178502363, compound

Product 1

HCID 178502280HCID 178502280, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of N-[(methyloxy)carbonyl]-L-alanine (22.5 mg, 0.153 mmol, prepared according to the procedure provided in WO2003055474) in DMF (2 mL) were added TEA (15.5 mg, 0.153 mmol) and HATU (58.2 mg, 0.153 mmol). After ˜3 min stirring, 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 (Example 19) (100 mg, 0.153 mmol) was introduced. After stirred for additional 2 hrs at rt, the reaction mixture was directly loaded to RP HPLC, eluting with 5 to 80% acetonitrile/water (0.2% NH3H2O (conc.)), to give methyl ((1S)-1-methyl-2-{(3S)-3-[4-(4′-{2-[(2S)-1-((2S)-3-methyl-2-{[(methyloxy)carbonyl]amino}butanoyl)-2-pyrrolidinyl]-1H-imidazol-4-yl}-4-biphenylyl)-1H-imidazol-2-yl]-6,10-dioxa-2-azaspiro[4.5]dec-2-yl}-2-oxoethyl)carbamate (Example 5) as solid (36 mg, yield: 29%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 10.04-11.11 (m, 2H) 7.37-8.02 (m, 8H) 7.18-7.36 (m, 2H) 5.60 (br. s., 2H) 5.17-5.40 (m, 2H) 3.17-4.73 (m, 14H) 2.79-3.19 (m, 1H) 2.45-2.81 (m, 1H) 2.29-2.45 (m, 1H) 1.49-2.29 (m, 8H) 1.22-1.47 (m, 3H) 0.73-1.16 (m, 6H). HRMS: (M+H)+ calcd: 783.3830. found: 783.3832.

Workup

  1. stirringAfter stirred for additional 2 hrs at rt
  2. washeluting with 5 to 80% acetonitrile/water (0.2% NH3H2O (conc.))

Sources & evidence

ORD record
ord-3f3b9f2a9bfa4aad84bb40d9728ffc6a
Source dataset
uspto-grants-2015_10
Patent number
US09150587B2

Reaction notes

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