Dimethylacetamide → HCID 86695347, compound

HRID 588975Notes

Reaction equation

HRID 588975 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C@@:10]3([CH2:18][C:17]4[C:12](=[CH:13][CH:14]=[C:15]([C:19]([OH:21])=[O:20])[CH:16]=4)[CH2:11]3)[C:9](=[O:22])[NH:8][C:5]2=[N:6][CH:7]=1.[CH3:23][N:24](C)C(=O)C>[C-]#N.[Zn+2].[C-]#N.[Zn].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:23]([C:2]1[CH:3]=[C:4]2[C@@:10]3([CH2:18][C:17]4[C:12](=[CH:13][CH:14]=[C:15]([C:19]([OH:21])=[O:20])[CH:16]=4)[CH2:11]3)[C:9](=[O:22])[NH:8][C:5]2=[N:6][CH:7]=1)#[N:24]

Participants

7

Reactant 2

HCID 31374DimethylacetamideHCID 69965971HCID 69965971, compound

Product 1

HCID 86695347HCID 86695347, compound

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
120 °C

Procedure

Argon was bubbled through a stirred mixture of (2R)-5′-bromo-2′-oxo-1,1′,2′,3-tetrahydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridine]-5-carboxylic acid (433 mg, 1.21 mmol), zinc cyanide (205 mg, 1.75 mmol), and zinc (31 mg, 0.47 mmol) in N,N-dimethylacetamide (10 mL) for 10 min. To the resulting mixture was added tris(dibenzylideneacetone)dipalladium(0) (27 mg, 0.030 mmol) and 1,1′-bis(diphenylphosphino)ferrocene (23 mg, 0.041 mmol) and argon was bubbled through the mixture for an additional 5 min. The reaction mixture was heated at 120° C. for 4 h, cooled to ambient temperature, and partitioned between EtOAc (100 mL) and 1 N aqueous hydrochloric acid (100 mL). The organic layer was washed with brine, then dried over sodium sulfate, filtered, and concentrated to dryness in vacuo. The residue was dissolved in a minimal volume of DMF and H2O was added to produce a precipitate. The precipitate was isolated by filtration, washing with H2O, and dried to give the title compound. MS: m/z=306.0 (M+1); 1H NMR (400 MHz, DMSO-d6) δ 12.81 (br s, 1H), 11.68 (s, 1H), 8.59 (d, 1H, J=1.9 Hz), 7.86-7.83 (m, 2H), 7.80 (dd, 1H, J=2.0, 0.5 Hz), 7.39 (d, 1H, J=8.3 Hz), 3.42-3.29 (m, 4H).

Workup

  1. customwas bubbled through the mixture for an additional 5 min
  2. temperaturecooled to ambient temperature
  3. custompartitioned between EtOAc (100 mL) and 1 N aqueous hydrochloric acid (100 mL)
  4. washThe organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness in vacuo
  8. dissolutionThe residue was dissolved in a minimal volume of DMF and H2O
  9. additionwas added
  10. customto produce a precipitate
  11. customThe precipitate was isolated by filtration
  12. washwashing with H2O
  13. customdried

Sources & evidence

ORD record
ord-3d10ffe08c584154b29f66c04a6db179
Source dataset
uspto-grants-2016_01
Patent number
US09227973B2

Reaction notes

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