Dimethylformamide → HCID 67111889, compound

HRID 1177615Notes

Reaction equation

HRID 1177615 reaction equation
CC(C)([O-])C.[Na+].[CH2:7]([O:9][C:10](=[O:21])[CH:11]([NH:17][C:18](=[O:20])[CH3:19])[C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH3:8].CN(C=O)C.Br[CH2:28][C:29]1[CH:34]=[CH:33][C:32]([C:35]2[S:36][C:37]3[C:42]([N:43]=2)=[CH:41][CH:40]=[C:39]([C:44]2([C:47]4[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=4)[CH2:46][CH2:45]2)[N:38]=3)=[C:31]([F:53])[CH:30]=1>C1COCC1.CCOC(C)=O>[C:18]([NH:17][C:11]([CH2:28][C:29]1[CH:34]=[CH:33][C:32]([C:35]2[S:36][C:37]3[C:42]([N:43]=2)=[CH:41][CH:40]=[C:39]([C:44]2([C:47]4[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=4)[CH2:45][CH2:46]2)[N:38]=3)=[C:31]([F:53])[CH:30]=1)([C:10]([O:9][CH2:7][CH3:8])=[O:21])[C:12]([O:14][CH2:15][CH3:16])=[O:13])(=[O:20])[CH3:19]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 14041Acetamidomalonic acid diethyl esterHCID 23676156Sodium t-butoxideHCID 67111838HCID 67111838, compound

Product 1

HCID 67111889HCID 67111889, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

In a sealable bottle, sodium tert-butoxide (0.120 g, 1.25 mmol) was added to a mixture of acetamidomalonic acid diethyl ester (0.272 g, 1.25 mmol) in THF (10.00 mL)/DMF (2.00 mL). The reaction mixture was heated to 80° C. for 20 min., cooled to ambient temperature, and a solution of 2-(4-(bromomethyl)-2-fluorophenyl)-5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine (0.500 g, 1.14 mmol) in THF 4 mL was added slowly dropwise. The resulting mixture was heated to reflux (90° C.) for 1.5 h, and the color changed from orange to yellow. The reaction mixture was cooled, poured over ice water, and treated with EtOAc. The organic layer was washed with water, NaCl, dried over MgSO4, filtered, and concentrated in vacuo. Purification by silica gel chromatography, 40 g column, 10-30% EtOAc/hexanes, followed by 30-50% (3% Et3N in EtOAc)/hexanes provided diethyl 2-acetamido-2-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)benzyl)malonate. MS (ESI) m/z: calculated: 575.2; Observed: 576.1 (M++1).

Workup

  1. temperaturecooled to ambient temperature
  2. temperatureThe resulting mixture was heated
  3. temperatureto reflux (90° C.) for 1.5 h
  4. temperatureThe reaction mixture was cooled
  5. washThe organic layer was washed with water, NaCl
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by silica gel chromatography, 40 g column, 10-30% EtOAc/hexanes

Sources & evidence

ORD record
ord-553ccc4a6b4f45db87fc236b87bc26d4
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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