Methanesulfonyl chloride → HCID 178493910, compound

HRID 536269Notes

Reaction equation

HRID 536269 reaction equation
[NH2:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][C:8]1[CH:9]=[CH:10][C:11]2[C:12]3[N:13]([CH2:29][CH2:30][N:31]=3)[C:14]([NH:20][C:21](=[O:28])[C:22]3[CH:27]=[CH:26][CH:25]=[N:24][CH:23]=3)=[N:15][C:16]=2[C:17]=1[O:18][CH3:19].C(N(CC)C(C)C)(C)C.[CH3:41][S:42](Cl)(=[O:44])=[O:43]>CN(C)C=O>[CH3:19][O:18][C:17]1[C:16]2[N:15]=[C:14]([NH:20][C:21](=[O:28])[C:22]3[CH:27]=[CH:26][CH:25]=[N:24][CH:23]=3)[N:13]3[CH2:29][CH2:30][N:31]=[C:12]3[C:11]=2[CH:10]=[CH:9][C:8]=1[O:7][CH2:6][CH2:5][O:4][CH2:3][CH2:2][NH:1][S:42]([CH3:41])(=[O:44])=[O:43]

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 178493908HCID 178493908, compound

Product 1

HCID 178493910HCID 178493910, compoundYield 12.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-{8-[2-(2-Aminoethoxy)-ethoxy]-7-methoxy-2,3-dihydro-imidazo[1,2-c]quinazolin-5-yl}-nicotinamide (Step 4, 75 mg, 0.18 mmol) was dissolved in dimethylformamide (2 mL). N,N-diisopropylethylamine (0.03 mL) was added, followed by methanesulfonyl chloride (0.01 mL, 0.14 mmol). The mixture was stirred at rt for 3 h, then was quenched by the addition of water. Saturated aqueous sodium bicarbonate was added, and the mixture was extracted several times with dichloromethane. The combined organic extracts were dried and concentrated to afford a residue, which was purified by preparative HPLC (gradient elution of 10-70% acetonitrile in water, 0.1% TFA). The product fractions were free based with saturated aqueous sodium bicarbonate, and the desired was isolated by extraction with dichloromethane. The organic layer was dried over sodium sulfate, and concentrated to give the title compound (8.7 mg, 12%). HPLC MS RT=1.79 min, MH+=503.2. 1H NMR (DMSO-d6+2 drops TFA-d) δ: 2.89 (3H, s), 3.11 (2H, t), 3.56 (2H, t), 3.85 (2H, m), 4.03 (3H, s), 4.26 (2H, m), 4.43 (2H, m), 4.57 (2H, m), 7.50 (1H, d), 7.86 (1H, m), 8.02 (1H, d), 8.83 (1H, m), 8.94 (1H, m), 9.47 (1H, m).

Workup

  1. customwas quenched by the addition of water
  2. additionSaturated aqueous sodium bicarbonate was added
  3. extractionthe mixture was extracted several times with dichloromethane
  4. customThe combined organic extracts were dried
  5. concentrationconcentrated
  6. customto afford a residue, which
  7. customwas purified by preparative HPLC (gradient elution of 10-70% acetonitrile in water, 0.1% TFA)
  8. customthe desired was isolated by extraction with dichloromethane
  9. dry with materialThe organic layer was dried over sodium sulfate
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-ec2f101f690e40ba8e349fd0ee3da5cd
Source dataset
uspto-grants-2014_10
Patent number
US08859572B2

Reaction notes

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