Aniline → HCID 86650288, compound

HRID 1615848Notes

Reaction equation

HRID 1615848 reaction equation
[CH2:1]([N:4]1[C:13](=[O:14])[C:8]2([CH2:12][CH2:11][CH2:10][CH2:9]2)[N:7]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:6][C@:5]1([C:23]1[CH:28]=[C:27]([F:29])[CH:26]=[C:25]([F:30])[CH:24]=1)[CH3:22])[CH:2]=[CH2:3].NC1C=C2C(=CC=1)C[C@]1(C3C(=NC=CC=3)NC1=O)C2.Br[C:51]1[CH:52]=[C:53]2[C:74](=[CH:75][CH:76]=1)[CH2:73][C:55]1([C:63]3[C:58](=[N:59][CH:60]=[CH:61][CH:62]=3)[N:57]([CH2:64][O:65][CH2:66][CH2:67][Si:68]([CH3:71])([CH3:70])[CH3:69])[C:56]1=[O:72])[CH2:54]2.NC1C=CC=CC=1.C([O-])(=O)C.[Na+]>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:29][C:27]1[CH:28]=[C:23]([C@@:5]2([CH3:22])[N:4]([CH2:1]/[CH:2]=[CH:3]/[C:76]3[CH:75]=[C:74]4[C:53](=[CH:52][CH:51]=3)[CH2:54][C:55]3([C:63]5[C:58](=[N:59][CH:60]=[CH:61][CH:62]=5)[N:57]([CH2:64][O:65][CH2:66][CH2:67][Si:68]([CH3:71])([CH3:69])[CH3:70])[C:56]3=[O:72])[CH2:73]4)[C:13](=[O:14])[C:8]3([CH2:12][CH2:11][CH2:10][CH2:9]3)[N:7]([C:15]([O:17][C:18]([CH3:21])([CH3:19])[CH3:20])=[O:16])[CH2:6]2)[CH:24]=[C:25]([F:30])[CH:26]=1

Participants

8

Reactant 5

HCID 6115AnilineHCID 517045Sodium AcetateHCID 53260812(R)-5-Amino-1,3-dihydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-oneHCID 58118694HCID 58118694, compoundHCID 58118695HCID 58118695, compound

Product 1

HCID 86650288HCID 86650288, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Procedure

A suspension of tert-butyl (8R)-9-allyl-8-(3,5-difluorophenyl)-8-methyl-10-oxo-6,9-diazaspiro[4.5]decane-6-carboxylate described in Intermediate 3 (0.292 g, 0.694 mmol) and 5-bromo-1′-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one described in Intermediate 13 (309 mg, 0.694 mmol Palladium(II) acetate (46.8 mg, 0.208 mmol), sodium acetate (0.57 mg, 0.694 mmol), and tris-2 methoxy phenyl phosphine (122 mg, 0.347 mmol), in DMF (3 ml) was microwaved at 130° C. for 1 hour. The mixture was filtered through a plug of celite, washing with water and ethyl acetate. The layers were separated, then the aqueous layer was washed with 3×30 mL EtOAc. The combine organic layers were washed with brine, then dried over sodium sulfate, filtered and concentrated in vacuo. The oily residue was purified on a 40 g redisep column, eluting with ethyl acetate:hexanes, 0:100 to 50:50. The desired fractions were concentrated in vacuo to yield the title compound. MS: m/z=785 (M+1).

Workup

  1. filtrationThe mixture was filtered through a plug of celite
  2. washwashing with water and ethyl acetate
  3. customThe layers were separated
  4. washthe aqueous layer was washed with 3×30 mL EtOAc
  5. washThe combine organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe oily residue was purified on a 40 g redisep column
  10. washeluting with ethyl acetate
  11. concentrationThe desired fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-d7673e50dadd4d889e856f9898bd1a9e
Source dataset
uspto-grants-2014_07
Patent number
US08765759B2

Reaction notes

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