Dichloromethane → HCID 89924168, compound

HRID 1505680Notes

Reaction equation

HRID 1505680 reaction equation
I[C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[CH:12][C:11]([C:14]3[CH:15]=[N:16][N:17]([CH:19]4[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]4)[CH:18]=3)=[CH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:32]([Si:34]([CH3:37])([CH3:36])[CH3:35])#[CH:33].C(Cl)Cl>C1COCC1.CN(C=O)C.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].[Cu]I>[C:28]([O:27][C:25]([N:22]1[CH2:23][CH2:24][CH:19]([N:17]2[CH:18]=[C:14]([C:11]3[CH:10]=[N:9][C:8]([C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([C:33]#[C:32][Si:34]([CH3:37])([CH3:36])[CH3:35])[CH:3]=4)=[N:13][CH:12]=3)[CH:15]=[N:16]2)[CH2:20][CH2:21]1)=[O:26])([CH3:31])([CH3:30])[CH3:29]

Participants

9

Reactant 3

HCID 6344DichloromethaneHCID 66111TrimethylsilylacetyleneHCID 89924119HCID 89924119, compound2×

Product 1

HCID 89924168HCID 89924168, compoundYield 39%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of tert-butyl 4-{4-[2-(3-iodophenyl)pyrimidin-5-yl]-1H-pyrazol-1-yl}piperidine-1-carboxylate (intermediate 18, 315 mg; 0.59 mmol; 1.0 eq.), Ethynyl-trimethyl-silane (83 μl; 0.59 mmol; 1.0 eq.), (dppf)PdCl2.CH2Cl2 (26 mg; 0.04 mmol; 0.06 eq.), CuI (7 mg; 0.04 mmol; 0.06 eq.) and TEA (115 μl; 0.89 mmol; 1.5 eq.) in dry THF (3.6 mL) and dry DMF (1 mL) was heated in a sealed vial at 80° C. for 48 h. The reaction mixture was then diluted with EtOAc and washed with sat. NH4Cl and brine. Organic phase was dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography on silica (heptanes:EtOAC, gradient form 90:10 to 50:50) afforded the title compound as a beige solid (115 mg, 39%). 1H NMR (300 MHz, DMSO-d6) d 9.17 (s, 2H), 8.57 (s, 1H), 8.41-8.38 (m, 1H), 8.15 (s, 2H), 7.61-7.54 (m, 2H), 4.08-4.03 (m, 2H), 2.96 (m, 2H9, 2.08-2.05 (m, 2H), 1.83-1.77 (m, 2H), 1.43 (s, 9H), 0.26 (s, 9H). MS (ESI+): 502.5.

Workup

  1. washwashed with sat. NH4Cl and brine
  2. dry with materialOrganic phase was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by flash chromatography on silica (heptanes:EtOAC, gradient form 90:10 to 50:50)

Sources & evidence

ORD record
ord-6cbe6fbc1a604dd29b0a4c2d99cfddfb
Source dataset
uspto-grants-2015_12
Patent number
US09216991B2

Reaction notes

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