Sodium hydride → HCID 178504768, compound

HRID 536275Notes

Reaction equation

HRID 536275 reaction equation
[OH:1][C:2]1[C:11]2[N:10]=[C:9]([NH:12][C:13](=[O:20])[C:14]3[CH:19]=[CH:18][CH:17]=[N:16][CH:15]=3)[N:8]3[CH2:21][CH2:22][N:23]=[C:7]3[C:6]=2[CH:5]=[CH:4][C:3]=1[O:24][CH2:25][CH2:26][CH2:27][N:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1.[H-].[Na+].Cl[CH2:37][C:38]1[CH:43]=[CH:42][C:41]([S:44]([CH3:47])(=[O:46])=[O:45])=[CH:40][CH:39]=1>CN(C=O)C>[CH3:47][S:44]([C:41]1[CH:42]=[CH:43][C:38]([CH2:37][O:1][C:2]2[C:11]3[N:10]=[C:9]([NH:12][C:13](=[O:20])[C:14]4[CH:19]=[CH:18][CH:17]=[N:16][CH:15]=4)[N:8]4[CH2:21][CH2:22][N:23]=[C:7]4[C:6]=3[CH:5]=[CH:4][C:3]=2[O:24][CH2:25][CH2:26][CH2:27][N:28]2[CH2:29][CH2:30][O:31][CH2:32][CH2:33]2)=[CH:39][CH:40]=1)(=[O:45])=[O:46]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1235301-(Chloromethyl)-4-methanesulfonylbenzeneHCID 178522494HCID 178522494, compound2×

Product 1

HCID 178504768HCID 178504768, compoundYield 70.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-[7-Hydroxy-8-(3-morpholin-4-ylpropoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]nicotinamide (Intermediate H, 0.09 g, 0.20 mmol) was suspended in DMF (2.0 mL) and NaH (0.02 g, 0.30 mmol, 60%) were added. After 20 min at rt 1-(chloromethyl)-4-(methylsulfonyl)benzene (0.06 g, 0.30 mmol) was added and the mixture was stirred at it for 16 h. The DMF was evaporated under reduced pressure and the residue triturated with a mixture of −10% MeOH in CH2Cl2 (4 mL). The mixture was vacuum filtered and the solids were washed well with CH2Cl2. The filtrate was concentrated under reduced pressure, and the residue purified via silica gel chromatography (0-6% MeOH/CH2Cl2). The fractions were combined, and the solvent was evaporated under reduced pressure. Drying under high vacuum gave the title compound (0.087 g, 70%): TLC (5% MeOH/CH2Cl2): Rf=0.47; HPLC MS RT=0.55 min, [M+Na]+=641; 1H NMR (DMSO-d6+2 drops TFA-d) δ: 2.21-2.35 (2H, m), 3.05-3.17 (2H, m), 3.22 (3H, s), 3.31 (2H, m), 3.42-3.52 (2H, m), 3.60-3.72 (2H, m), 3.94-4.04 (2H, m), 4.29 (2H, m), 4.39 (2H, t), 4.56 (2H, m), 5.37 (2H, s), 7.52 (1H, d), 7.72 (1H, dd), 7.85 (2H, d), 8.01 (2H, d), 8.10 (1H, d), 8.66 (1H, d), 8.89 (1H, dd), 9.43 (1H, s).

Workup

  1. customThe DMF was evaporated under reduced pressure
  2. customthe residue triturated with a mixture of −10% MeOH in CH2Cl2 (4 mL)
  3. filtrationfiltered
  4. washthe solids were washed well with CH2Cl2
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue purified via silica gel chromatography (0-6% MeOH/CH2Cl2)
  7. customthe solvent was evaporated under reduced pressure
  8. customDrying under high vacuum

Sources & evidence

ORD record
ord-7b43efd286dd47259b9b0477b5152355
Source dataset
uspto-grants-2014_10
Patent number
US08859572B2

Reaction notes

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