Sodium hydride → HCID 118523423, compound

HRID 1486957Notes

Reaction equation

HRID 1486957 reaction equation
[N:1]1([CH2:7][CH2:8][CH2:9][OH:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[F:13][C:14]1[C:15]([C:35]2[CH:36]=[N:37][C:38](F)=[CH:39][CH:40]=2)=[CH:16][C:17]2[C:18]3[N:26]([CH:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)[C:25](=[O:33])[N:24]([CH3:34])[C:19]=3[CH:20]=[N:21][C:22]=2[CH:23]=1>C1COCC1>[F:13][C:14]1[C:15]([C:35]2[CH:36]=[N:37][C:38]([O:10][CH2:9][CH2:8][CH2:7][N:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)=[CH:39][CH:40]=2)=[CH:16][C:17]2[C:18]3[N:26]([CH:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[C:25](=[O:33])[N:24]([CH3:34])[C:19]=3[CH:20]=[N:21][C:22]=2[CH:23]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 66032Piperidine-1-propanolHCID 118502145HCID 118502145, compound

Product 1

HCID 118523423HCID 118523423, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

3-(Piperidin-1-yl)propan-1-ol (0.053 mL, 0.35 mmol) was added slowly to a slurry of sodium hydride (31.5 mg, 0.79 mmol) in THF (7 mL) and the solution stirred at ambient temperature for 30 minutes. 7-Fluoro-8-(6-fluoro-3-pyridyl)-3-methyl-1-tetrahydropyran-4-yl-imidazo[4,5-c]quinolin-2-one (125 mg, 0.32 mmol) in THF (3 mL) was added to the reaction mixture via syringe over a period of 1 minute and the reaction stirred for 24 h. The reaction was quenched with water then extracted into DCM, the organic phase separated and concentrated in vacuo. The crude product was purified by FCC, elation gradient 0 to 10% 1M methanolic ammonia in DCM, and the resultant oil triturated with Et2O to afford the desired material as a white solid (92 mg, 56%). NMR Spectrum: 1H NMR (500 MHz, CDCl3) δ 1.38-1.52 (2H, m), 1.61 (4H, p), 1.92 (2H, dd), 2.03 (2H, dt), 2.43 (4H, s), 2.47-2.58 (2H, m), 2.94 (2H, d), 3.53-3.63 (5H, m), 4.22 (2H, dd), 4.42 (2H, t), 5.01 (1H, s), 6.89 (1H, dd), 7.85-7.96 (2H, m), 8.26 (1H, s), 8.44 (1H, s), 8.71 (1H, s). Mass Spectrum: m/z (ES+)[M+H]+=520.

Workup

  1. stirringthe reaction stirred for 24 h
  2. customThe reaction was quenched with water
  3. extractionthen extracted into DCM
  4. customthe organic phase separated
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by FCC, elation gradient 0 to 10% 1M methanolic ammonia in DCM
  7. customthe resultant oil triturated with Et2O

Sources & evidence

ORD record
ord-81145d955f8649a7a38cb312b6dbe659
Source dataset
uspto-grants-2016_08
Patent number
US09428503B2

Reaction notes

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