Potassium → HCID 59585183, compound

HRID 658971Notes

Reaction equation

HRID 658971 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@H:9]1[CH2:15][N:14]([CH2:16][C:17]([F:20])([F:19])[F:18])[C:13](=[O:21])[C@H:12]([NH:22][C:23]([N:25]2[CH2:30][CH2:29][CH:28]([N:31]3[C:39]4[C:34](=[N:35][CH:36]=[CH:37][CH:38]=4)[NH:33][C:32]3=[O:40])[CH2:27][CH2:26]2)=[O:24])[CH2:11][CH2:10]1.[K].[P:42]([O:60][CH2:61]Cl)([O:52][CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)([O:44][CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)=[O:43]>>[P:42]([O:60][CH2:61][N:33]1[C:34]2=[N:35][CH:36]=[CH:37][CH:38]=[C:39]2[N:31]([CH:28]2[CH2:29][CH2:30][N:25]([C:23]([NH:22][C@@H:12]3[CH2:11][CH2:10][C@@H:9]([C:3]4[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=4[F:1])[CH2:15][N:14]([CH2:16][C:17]([F:18])([F:19])[F:20])[C:13]3=[O:21])=[O:24])[CH2:26][CH2:27]2)[C:32]1=[O:40])([O:44][CH2:45][C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1)([O:52][CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)=[O:43]

Participants

4

Reactant 3

HCID 5462222PotassiumHCID 11319053TelcagepantHCID 11484214Dibenzyl chloromethyl phosphate

Product 1

HCID 59585183HCID 59585183, compound

Procedure

To a stirred solution of N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyri din-1-yl)piperidine-1-carboxamide, potassium salt, [Burgey et al. U.S. Pat. No. 6,953,790 B2] (1.00 g, 1.65 mmol) in anhydrous, degassed DMF (200 mL) at ambient temperature was added dibenzyl chloromethyl phosphate [Mäntylä et al. Tetrahedron Lett. 2002, 43, 3793] (0.54 g, 1.65 mmol). The resulting mixture was stirred at ambient temperature for 4 h, filtered, and purified by preparative HPLC on a C18 reversed phase column, eluting with a gradient of H2O:CH3CN:CF3CO2H—90:10:0.1 to 0:100:0.1. The product-containing fractions were poured into saturated aqueous NaHCO3 and extracted with EtOAc (2×50 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo to give the title compound. MS: m/z=857.7 (M+1).

Workup

  1. custom6,953,790 B2] (1.00 g, 1.65 mmol) in anhydrous, degassed DMF (200 mL) at ambient temperature
  2. filtrationfiltered
  3. custompurified by preparative HPLC on a C18
  4. washeluting with a gradient of H2O
  5. additionThe product-containing fractions were poured into saturated aqueous NaHCO3
  6. extractionextracted with EtOAc (2×50 mL)
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-85434ffa0e1f41ab8d59df6ad2bffa51
Source dataset
uspto-grants-2011_12
Patent number
US08080544B2

Reaction notes

Loading…