Sodium hydride → HCID 11330771, compound

HRID 2099745Notes

Reaction equation

HRID 2099745 reaction equation
[H-].[Na+].[OH:3][NH:4][C:5](=[NH:13])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.CO[C:16](=O)[CH:17]([NH:29][C:30]([N:32]1[CH2:37][CH2:36][CH:35]([N:38]2[CH2:47][C:46]3[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=3)[NH:40][C:39]2=[O:48])[CH2:34][CH2:33]1)=[O:31])[CH2:18][C:19]1[CH:20]=[C:21]2[C:25](=[C:26]([CH3:28])[CH:27]=1)[NH:24][N:23]=[CH:22]2>O1CCCC1>[CH2:6]([C:5]1[N:13]=[C:16]([CH:17]([NH:29][C:30]([N:32]2[CH2:33][CH2:34][CH:35]([N:38]3[CH2:47][C:46]4[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=4)[NH:40][C:39]3=[O:48])[CH2:36][CH2:37]2)=[O:31])[CH2:18][C:19]2[CH:20]=[C:21]3[C:25](=[C:26]([CH3:28])[CH:27]=2)[NH:24][N:23]=[CH:22]3)[O:3][N:4]=1)[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 24862915(+/-)-3-(7-Methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid methyl esterHCID 178510798HCID 178510798, compound

Product 1

HCID 11330771HCID 11330771, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

Sodium hydride (8 mg, 0.366 mmol) was added to a solution of N-hydroxy-2-phenyl-acetamidine (50 mg, 0.366 mmol) in tetrahydrofuran (15 mL). The solution was stirred at 60° C. for 15 min. A solution of (±)-3-(7-methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid methyl ester (60 mg, 0.122 mmol) in tetrahydrofuran (5 mL) was added. The reaction mixture was stirred at 60° C. for 18 h. The reaction was then cooled to room temperature and the solvent removed under reduced pressure. The residue was dissolved with methylene chloride and partitioned with water and extracted with methylene chloride (3×50 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated under reduce pressure. Purification was carried out by preparative HPLC. LC/MS: tR=1.79 min, 591 (MH)+.

Workup

  1. stirringThe reaction mixture was stirred at 60° C. for 18 h
  2. temperatureThe reaction was then cooled to room temperature
  3. customthe solvent removed under reduced pressure
  4. dissolutionThe residue was dissolved with methylene chloride
  5. custompartitioned with water
  6. extractionextracted with methylene chloride (3×50 mL)
  7. dry with materialThe organic layer was dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification

Sources & evidence

ORD record
ord-af719b5dd8474015a7cc1213c65504e2
Source dataset
uspto-grants-2009_08
Patent number
US07569578B2

Reaction notes

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