Sodium hydride → HCID 178496647, compound

HRID 1486953Notes

Reaction equation

HRID 1486953 reaction equation
[N:1]1([CH2:6][CH2:7][CH2:8][OH:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[F:12][C:13]1[C:14]([C:34]2[CH:35]=[N:36][C:37](F)=[CH:38][CH:39]=2)=[CH:15][C:16]2[C:17]3[N:25]([C@H:26]4[CH2:29][C@@H:28]([O:30][CH3:31])[CH2:27]4)[C:24](=[O:32])[N:23]([CH3:33])[C:18]=3[CH:19]=[N:20][C:21]=2[CH:22]=1>C1COCC1>[F:12][C:13]1[C:14]([C:34]2[CH:35]=[N:36][C:37]([O:9][CH2:8][CH2:7][CH2:6][N:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)=[CH:38][CH:39]=2)=[CH:15][C:16]2[C:17]3[N:25]([C@H:26]4[CH2:29][C@@H:28]([O:30][CH3:31])[CH2:27]4)[C:24](=[O:32])[N:23]([CH3:33])[C:18]=3[CH:19]=[N:20][C:21]=2[CH:22]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2093421-PyrrolidinepropanolHCID 178496646HCID 178496646, compound

Product 1

HCID 178496647HCID 178496647, compoundYield 39.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-(Pyrrolidin-1-yl)propan-1-ol (46.9 mg, 0.36 mmol) was added to sodium hydride (29.1 mg, 1.21 mmol) in THF (4 mL) at ambient temperature over a period of 20 minutes. 7-Fluoro-8-(6-fluoropyridin-3-yl)-1-(cis-3-methoxycyclobutyl)-3-methylimidazo[4,5-c]quinolin-2-one (120 mg, 0.30 mmol) was added. The resulting mixture was stirred at ambient temperature for 2 h. The reaction mixture was quenched with water and the crude product purified by FCC, elution gradient 0 to 5% MeOH in DCM. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 0.1% formic acid) and MeCN as eluents. Fractious containing the desired compound were evaporated to dryness to afford the desired material (60.0 mg, 38.7%) as a off-white solid. NMR Spectrum: 1H NMR (300 MHz, MeOD) δ 1.90-2.00 (4H, m), 2.10-2.20 (2H, m), 2.81-3.00 (8H, m), 3.04-3.17 (2H, m), 3.28 (3H, s), 3.6 (3H, s), 3.85-3.96 (1H, m), 4.48 (2H, t), 5.00-5.13 (1H, m), 6.88 (1H, d), 7.82 (1H, d), 8.05 (1H, d), 8.43-8.50 (2H, m), 8.83 (1H, s) Mass Spectrum: m/z (ES+)[M+H]+=506.

Workup

  1. customThe reaction mixture was quenched with water
  2. customthe crude product purified by FCC, elution gradient 0 to 5% MeOH in DCM
  3. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
  4. additionFractious containing the desired compound
  5. customwere evaporated to dryness

Sources & evidence

ORD record
ord-2193c8a442644c22a21debbf1dfe6353
Source dataset
uspto-grants-2016_08
Patent number
US09428503B2

Reaction notes

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