Dimethylformamide → HCID 69810882, compound

HRID 529070Notes

Reaction equation

HRID 529070 reaction equation
Br[C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[C:4]2[N:9]([C:24]3[C:25]4[C@H:32]([CH3:33])[CH2:31][CH2:30][C:26]=4[N:27]=[CH:28][N:29]=3)[CH2:10][C:11]3([CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]3)[C:3]=12.[CH3:34][N:35](C=O)C>O.[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:8][C:7]1[C:2]([C:34]#[N:35])=[C:3]2[C:11]3([CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]3)[CH2:10][N:9]([C:24]3[C:25]4[C@H:32]([CH3:33])[CH2:31][CH2:30][C:26]=4[N:27]=[CH:28][N:29]=3)[C:4]2=[CH:5][CH:6]=1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 69812757HCID 69812757, compound

Product 1

HCID 69810882HCID 69810882, compoundYield 33%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

To a solution (R)-tert-butyl 4-bromo-5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-carboxylate (0.200 g, 0.375 mmol) in DMF (2 mL) was added zinc cyanide (0.088 g, 0.75 mmol) and tetrakis(triphenylphosphine)palladium (0) (0.022 g, 0.019 mmol). The mixture was heated at about 95° C. for 2 days. After cooling, the mixture was diluted with water and extracted with EtOAc. The combined organic layers were washed with saturated aqueous NaHCO3 solution and brine, dried and concentrated. The residue was purified by flash chromatography on silica gel (EtOAc hexanes, 1:1) to give (R)-tert-butyl 5-chloro-4-cyano-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-carboxylate (0.060 g, 33%) as a oil. LCMS (APCI+) m/z 480, 482 [M+H]+; Rt=4.51 min.

Workup

  1. temperatureAfter cooling
  2. extractionextracted with EtOAc
  3. washThe combined organic layers were washed with saturated aqueous NaHCO3 solution and brine
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography on silica gel (EtOAc hexanes, 1:1)

Sources & evidence

ORD record
ord-da82c1d809d846bfa21fe7ea31684320
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

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