Trifluoroacetic acid → (6S)-3-{3-[(8R)-8-(3,5-Difluorophenyl)-6-(2-fluoroethyl)-8-methyl-10-oxo-6,9-diazaspiro[4.5] dec-9-yl]prop-1-yn-1-yl}-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

HRID 1615859Notes

Reaction equation

HRID 1615859 reaction equation
Cl[CH2:2][CH2:3][N:4]1[CH2:13][C@:12]([C:15]2[CH:20]=[C:19]([F:21])[CH:18]=[C:17]([F:22])[CH:16]=2)([CH3:14])[N:11]([CH2:23][C:24]#[C:25][C:26]2[CH:27]=[C:28]3[CH2:43][C@@:33]4([C:41]5[C:36](=[N:37][CH:38]=[CH:39][CH:40]=5)[NH:35][C:34]4=[O:42])[CH2:32][C:29]3=[N:30][CH:31]=2)[C:10](=[O:44])[C:5]21[CH2:9][CH2:8][CH2:7][CH2:6]2.C(O)(C(F)(F)[F:48])=O>C(#N)C.[Ag]F>[F:21][C:19]1[CH:20]=[C:15]([C@@:12]2([CH3:14])[N:11]([CH2:23][C:24]#[C:25][C:26]3[CH:27]=[C:28]4[CH2:43][C@@:33]5([C:41]6[C:36](=[N:37][CH:38]=[CH:39][CH:40]=6)[NH:35][C:34]5=[O:42])[CH2:32][C:29]4=[N:30][CH:31]=3)[C:10](=[O:44])[C:5]3([CH2:6][CH2:7][CH2:8][CH2:9]3)[N:4]([CH2:3][CH2:2][F:48])[CH2:13]2)[CH:16]=[C:17]([F:22])[CH:18]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66865111(6S)-3-{3-[(8R)-6-(2-Chloroethyl)-8-(3,5-difluorophenyl)-8-methyl-10-oxo-6,9-diazaspiro[4.5]dec-9-yl]prop-1-yn-1-yl}-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

Product 1

HCID 58118709(6S)-3-{3-[(8R)-8-(3,5-Difluorophenyl)-6-(2-fluoroethyl)-8-methyl-10-oxo-6,9-diazaspiro[4.5] dec-9-yl]prop-1-yn-1-yl}-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

Reagents, catalysts & solvents 2

HCID 62656Caswell No. 736CatalystHCID 6342AcetonitrileSolvent

Procedure

A solution of (6S)-3-{3-[(8R)-6-(2-chloroethyl)-8-(3,5-difluorophenyl)-8-methyl-10-oxo-6,9-diazaspiro[4.5] dec-9-yl]prop-1-yn-1-yl}-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one from Step A (67 mg, 0.11 mmol) and silver(I)fluoride (140 mg, 1.1 mmol) in acetonitrile (3 ml) was heated at 100° C. for 90 min The mixture was diluted with TFA (0.5 mL), filtered, and purified directly by HPLC using a reversed phase C18 column and eluting with a gradient of H2O:CH3CN:CF3CO2H—90:10:0.1 to 5:95:0.1. The desired fractions were poured onto saturated NaHCO3 (10 mL) and extracted with CH2Cl2 (3×10 ml). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo to yield the title compound. MS: m/z=600 (M+1). HRMS: m/z=600.2604 (M+1); calculated m/z=600.2581 (M+1) for C34H34F3N5O2.

Workup

  1. filtrationfiltered
  2. custompurified directly by HPLC
  3. washeluting with a gradient of H2O
  4. additionThe desired fractions were poured onto saturated NaHCO3 (10 mL)
  5. extractionextracted with CH2Cl2 (3×10 ml)
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-abecab5383284c299f73ec99b40c847b
Source dataset
uspto-grants-2014_07
Patent number
US08765759B2

Reaction notes

Loading…