Sodium Carbonate → HCID 59275217, compound

HRID 1877550Notes

Reaction equation

HRID 1877550 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[NH2:6][C:7]1[C:26]([C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([C:33](=[O:44])[NH:34][C:35]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)([CH3:37])[CH3:36])[CH:28]=2)=[CH:25][C:10]2[C:11]([C:21]([NH:23][CH3:24])=[O:22])=[C:12]([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=3)[O:13][C:9]=2[CH:8]=1.Br[CH2:46][CH2:47][O:48][Si](C(C)(C)C)(C)C.C([O-])([O-])=O.[Na+].[Na+]>N1C=CC=CC=1.CCOC(C)=O>[F:20][C:17]1[CH:16]=[CH:15][C:14]([C:12]2[O:13][C:9]3[CH:8]=[C:7]([N:6]([CH2:46][CH2:47][OH:48])[S:2]([CH3:1])(=[O:4])=[O:3])[C:26]([C:27]4[CH:32]=[CH:31][CH:30]=[C:29]([C:33](=[O:44])[NH:34][C:35]([C:38]5[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=5)([CH3:37])[CH3:36])[CH:28]=4)=[CH:25][C:10]=3[C:11]=2[C:21]([NH:23][CH3:24])=[O:22])=[CH:19][CH:18]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 31297Methanesulfonyl chlorideHCID 3608067(2-Bromoethoxy)-tert-butyldimethylsilaneHCID 59275126HCID 59275126, compound

Product 1

HCID 59275217HCID 59275217, compoundYield 40.5%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

Step 1: methanesulfonyl chloride (10 μL, 0.128 mmol) was added to a stirring solution of 6-amino-2-(4-fluorophenyl)-N-methyl-5-(3-(2-phenylpropan-2-ylcarbamoyl)phenyl)benzofuran-3-carboxamide (50 mg, 0.096 mmol) in pyridine (1 mL) at rt. It was allowed to stir for 2 hours and then concentrated and diluted with EtOAc and washed with sat NaHCO3, and sat NaCl. The organic phase was dried over Na2SO4, filtered and concentrated. Step 2: The crude residue was dissolved in DMF (1 mL) and treated with (2-bromoethoxy)(tert-butyl)dimethylsilane (102 μL, 0.479 mmol) and Na2CO3 (31 mg, 0.288 mmol) at rt. It was heated to 100° C. for 4 hours and then diluted with EtOAc and washed with sat NaHCO3, and sat NaCl. The organic phase was dried over Na2SO4, filtered and concentrated. Step 3: The crude residue was taken up in THF (2 mL) and treated with 2 mL of 1N HCl. and allowed to stir at rt for 1 hr. The mixture was diluted with EtOAc and washed with sat NaHCO3, and sat NaCl. The organic phase was dried over Na2SO4, filtered and concentrated and triturated with Et2O to give the titled compound (25 mg, 39%). 1H NMR (500 MHz, CD3OD) δ ppm 8.14-8.21 (1H, m), 7.95-8.04 (2H, m), 7.83-7.87 (1H, m), 7.76-7.81 (1H, m), 7.66-7.74 (2H, m), 7.56 (1H, t, J=7.63 Hz), 7.41-7.49 (2H, m), 7.24-7.33 (4H, m), 7.17 (1H, t, J=7.32 Hz), 2.94 (3H, s), 1.76 (6H, s). LC-MS retention time 1.42 min; m/z (MH+): 644. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters XBridge 5 u C18 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 5% acetonitrile/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% acetonitrile/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode. Additional HPLC method: Solvent A=5% CH3CN/95% H2O/0.1% TFA, Solvent B=95% CH3CN/5% H2O/0.1% TFA, Start % B=10, Final % B=100, Gradient time=15 min, Stop time=18 min, Flow Rate=1 ml/min. Column: Waters Sunfire C-18, 4.6×150 mm, 3.5 μm, Rt=12.26 min, purity=96%; Additional HPLC method: Solvent A=5% MeOH/95% H2O/10 mM ammonium bicarbonate, Solvent B=95% MeOH/5% H2O/10 mM ammonium bicarbonate, Start % B=10, Final % B=100, Gradient time=15 min, Stop time=18 min, Flow Rate=1 ml/min. Column: Phenomenex Gemini C-18, 4.6×150 mm, 3 μm, Rt=13.61 min, purity=94%.

Workup

  1. concentrationconcentrated
  2. additiondiluted with EtOAc
  3. washwashed
  4. dry with materialThe organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionStep 2: The crude residue was dissolved in DMF (1 mL)
  8. washwashed
  9. dry with materialThe organic phase was dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. additiontreated with 2 mL of 1N HCl
  13. stirringto stir at rt for 1 hr
  14. additionThe mixture was diluted with EtOAc
  15. washwashed
  16. dry with materialThe organic phase was dried over Na2SO4
  17. filtrationfiltered
  18. concentrationconcentrated
  19. customtriturated with Et2O

Sources & evidence

ORD record
ord-df6c57c5125d453f94aad7c1400cf6e1
Source dataset
uspto-grants-2012_11
Patent number
US08309558B2

Reaction notes

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