HCID 86660245, compound → HCID 46178835, compound

HRID 1890713Notes

Reaction equation

HRID 1890713 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@@H:9]([NH:20][CH2:21][C:22]2[CH:23]=[N:24][C:25]3[C:30]([CH:31]=2)=[CH:29][C:28]2[CH2:32][C@:33]4([CH2:43][C:27]=2[CH:26]=3)[C:41]2[C:36](=[N:37][CH:38]=[CH:39][CH:40]=2)[NH:35][C:34]4=[O:42])[CH2:10][CH2:11][C:12]([CH3:19])([CH3:18])[C:13](OCC)=[O:14])[CH:5]=[C:6]([F:8])[CH:7]=1>C(Cl)(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([C@H:9]2[N:20]([CH2:21][C:22]3[CH:23]=[N:24][C:25]4[C:30]([CH:31]=3)=[CH:29][C:28]3[CH2:32][C@:33]5([CH2:43][C:27]=3[CH:26]=4)[C:41]3[C:36](=[N:37][CH:38]=[CH:39][CH:40]=3)[NH:35][C:34]5=[O:42])[C:13](=[O:14])[C:12]([CH3:19])([CH3:18])[CH2:11][CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

3

Reactant 1

HCID 86660245HCID 86660245, compound

Product 1

HCID 46178835HCID 46178835, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
140 °C

Procedure

A solution of ethyl (5S)-5-(3,5-difluorophenyl)-2,2-dimethyl-5-({[(7S)-2′-oxo-1′,2′,6,8-tetrahydrospiro[cyclopenta[g]quinoline-7,3′-pyrrolo[2,3-b]pyridin]-3-yl]methyl}amino)pentanoate from Step B (131 mg, 0.224 mmol) in a 90/10 mixture of xylenes/HOAc (20 mL) was heated to 140° C. for ˜22 hours. After allowing the reaction mixture to cool, the bulk of the solvent was removed in vacuo to give a residue. This residue was diluted with chloroform (50 mL) and washed with saturated sodium bicarbonate (25 mL). This aqueous layer was then extracted twice with DCM (2×30 mL). The combined organics were dried over sodium sulfate, filtered and concentrated in vacuo to provide a residue. This residue was applied to a silica gel column for purification, eluting with a gradient of CH2Cl2:MeOH—99:1 to 94:6. Clean product-containing fractions were pooled and concentrated in vacuo to give the title compound. MS: m/z=585 (M+1). HRMS: m/z=539.2264; calculated m/z=539.2253 for C32H29F2N4O2.

Workup

  1. temperatureto cool
  2. customthe bulk of the solvent was removed in vacuo
  3. customto give a residue
  4. washwashed with saturated sodium bicarbonate (25 mL)
  5. extractionThis aqueous layer was then extracted twice with DCM (2×30 mL)
  6. dry with materialThe combined organics were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto provide a residue
  10. customThis residue was applied to a silica gel column for purification
  11. washeluting with a gradient of CH2Cl2
  12. additionClean product-containing fractions
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-32bd107e59f44cc38f4279c9e7ca0cf5
Source dataset
uspto-grants-2013_08
Patent number
US08507477B2

Reaction notes

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