Diiodomethane → HCID 89924119, compound

HRID 1505672Notes

Reaction equation

HRID 1505672 reaction equation
N(OCCC(C)C)=O.N[C:10]1[CH:11]=[C:12]([C:16]2[N:21]=[CH:20][C:19]([C:22]3[CH:23]=[N:24][N:25]([CH:27]4[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]4)[CH:26]=3)=[CH:18][N:17]=2)[CH:13]=[CH:14][CH:15]=1.[I:40]CI>C1COCC1.[Cu]I>[I:40][C:10]1[CH:11]=[C:12]([C:16]2[N:21]=[CH:20][C:19]([C:22]3[CH:23]=[N:24][N:25]([CH:27]4[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]4)[CH:26]=3)=[CH:18][N:17]=2)[CH:13]=[CH:14][CH:15]=1

Participants

6

Reactant 3

HCID 6346DiiodomethaneHCID 8053Isoamyl NitriteHCID 89924531HCID 89924531, compound2×

Product 1

HCID 89924119HCID 89924119, compoundYield 78.4%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

Isopentyl nitrite (192 μl; 1.43 mmol; 3.0 eq.) was added to a solution of tert-butyl 4-4-[2-(3-aminophenyl)pyrimidin-5-yl]-1H-pyrazol-1-ylpiperidine-1-carboxylate (intermediate 5, step 1, 200 mg; 0.48 mmol; 1.0 eq.), Copper(I) iodide (91 mg; 0.48 mmol; 1.0 eq.) and diiodomethane (193 μl; 2.38 mmol; 5.0 eq.) in dry THF (8.0 mL) and the reaction mixture was refluxed for 2 hours. The reaction mixture was filtered through a Celite pad and the filtrate was concentrated to dryness. Purification by flash chromatography (EtOAc:heptane, gradient from 20:80 to 50:50) afforded the title compound as a white solid (200 mg; 67%). 1H NMR (300 Mz, DMSO-d6) δ 9.17 (s, 2H), 8.71 (t, J=1.7 Hz, 1H), 8.56 (s, 1H), 8.40-8.37 (m, 1H), 8.15 (s, 1H), 7.90-7.86 (m, 1H), 7.35 (t, J=7.9 Hz, 1H), 4.48-4.38 (m, 1H), 4.08-4.03 (m, 2H), 2.95 (m, 2H), 2.08-2.05 (m, 2H), 1.87-1.73 (m, 2H), 1.43 (s, 9H). HPLC (Condition A): Rt 5.47 min (purity 91.0%). MS (ESI+): 532.4

Workup

  1. temperaturethe reaction mixture was refluxed for 2 hours
  2. filtrationThe reaction mixture was filtered through a Celite pad
  3. concentrationthe filtrate was concentrated to dryness
  4. customPurification by flash chromatography (EtOAc:heptane, gradient from 20:80 to 50:50)

Sources & evidence

ORD record
ord-b9d715b95f824769992ca127821b2f01
Source dataset
uspto-grants-2015_12
Patent number
US09216991B2

Reaction notes

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