HCID 118598561, compound → HCID 118599084, compound

HRID 1050395Notes

Reaction equation

HRID 1050395 reaction equation
COC1C=CC(COC2C(=O)[N:13]3[C:16]4(CCCCC4)[NH:17][C:18](=[O:19])[C:12]3=[C:11]([CH3:25])C=2)=CC=1.[CH2:28]([Li])CCC.Cl[C:34]1[CH:39]=[C:38](NC2N=CN=C(NC(C3CC3)=O)C=2)[C:37](=[O:53])[N:36]2[C:54]([C:59]3[CH:64]=[CH:63][CH:62]=C(F)C=3)([CH3:58])[NH:55][C:56](=[O:57])[C:35]=12>O1CCCC1>[CH3:28][C:34]1[CH:39]=[C:38]([C:18]([C:12]2[CH:11]=[CH:25][N:17]=[CH:16][N:13]=2)=[O:19])[C:37](=[O:53])[N:36]2[C:54]3([CH2:58][CH2:62][CH2:63][CH2:64][CH2:59]3)[NH:55][C:56](=[O:57])[C:35]=12

Participants

5

Reactant 3

HCID 118598561HCID 118598561, compoundHCID 118598862HCID 118598862, compoundHCID 178418339Butyllithium

Product 1

HCID 118599084HCID 118599084, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6′-bromo-8′-methyl-2′H-spiro[cyclohexane-1,3′-imidazo[1,5-c]pyridine]-1′,5′-dione (2, 0.3 g, 0.96 mmol) in tetrahydrofuran (25 mL), n-butyllithium (0.58 g, 2.89 mmol) was added at −78° C. The reaction mixture was stirred for 30 min. To the mixture N-methoxy-N-methylpyrimidine-4-carboxamide (1, 0.25 g, 1.44 mmol) was added at −78° C. and then the mixture was stirred at room temperature for 16 h. After completion, the reaction was quenched with aqueous solution of ammonium chloride (50 mL) and extracted with dichloromethane (2×50 mL). The organic layer was separated and was hed with brine (25 mL) and the solvent was evaporated under reduced pressure. The crude was purified by silica gel (220-400 mesh) column chromatography using 0.5% methanol in dichloromethane as eluent. The fractions were concentrated to afford 8′-methyl-6′-(pyrimidine-4-carbonyl)-2′H-spiro[cyclohexane-1,3′-imidazo[1,5-a]pyridine]-1′,5′-dione as yellow solid. Yield: 0.001 g, 3.0%; MS (ESI) m/z 339.13 [M+1]+; 1H NMR (400 MHz, DMSO-d6) δ 10.58 (s, 1H), 9.26 (s, 1H), 9.07 (d, J=5.08 Hz, 1H), 9.97 (s, 1H), 7.83 (d, J=5.2 Hz, 1H), 2.85-2.75 (m, 2H), 2.45 (s, 3H), 1.68-162 (m, 2H), 1.60-1.53 (m, 3H), 1.46-1.43 (m, 2H), 1.10-1.09 (m, 1H).

Workup

  1. stirringthe mixture was stirred at room temperature for 16 h
  2. customAfter completion, the reaction was quenched with aqueous solution of ammonium chloride (50 mL)
  3. extractionextracted with dichloromethane (2×50 mL)
  4. customThe organic layer was separated
  5. customthe solvent was evaporated under reduced pressure
  6. customThe crude was purified by silica gel (220-400 mesh) column chromatography
  7. concentrationThe fractions were concentrated

Sources & evidence

ORD record
ord-0fa6cda7d5ab441aa85dc067d32125c4
Source dataset
uspto-grants-2016_07
Patent number
US09382248B2

Reaction notes

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