Water → Tert-butyl 5-(2-bromo-4-cyanophenylamino)-3-formylpyrazolo[1,5-a]pyrimidin-7-yl(cyclopropyl)carbamate

HRID 624798Notes

Reaction equation

HRID 624798 reaction equation
Cl[C:2]1[CH:7]=[C:6]([N:8]([CH:16]2[CH2:18][CH2:17]2)[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[N:5]2[N:19]=[CH:20][C:21]([CH:22]=[O:23])=[C:4]2[N:3]=1.[NH2:24][C:25]1[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[CH:27][C:26]=1[Br:33].CC(C)([O-])C.[Na+].O>C1COCC1>[Br:33][C:26]1[CH:27]=[C:28]([C:29]#[N:30])[CH:31]=[CH:32][C:25]=1[NH:24][C:2]1[CH:7]=[C:6]([N:8]([CH:16]2[CH2:18][CH2:17]2)[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[N:5]2[N:19]=[CH:20][C:21]([CH:22]=[O:23])=[C:4]2[N:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 15152794-Amino-3-bromobenzonitrileHCID 23676156Sodium t-butoxideHCID 58196421Tert-butyl 5-chloro-3-formylpyrazolo[1,5-a]pyrimidin-7-yl(cyclopropyl)carbamate

Product 1

HCID 86714612Tert-butyl 5-(2-bromo-4-cyanophenylamino)-3-formylpyrazolo[1,5-a]pyrimidin-7-yl(cyclopropyl)carbamateYield 32%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Tert-butyl 5-chloro-3-formylpyrazolo[1,5-a]pyrimidin-7-yl(cyclopropyl)carbamate (225 mg, 0.67 mmol) and 4-amino-3-bromobenzonitrile (197 mg, 1 mmol) were dissolved in anhydrous THF (4.5 mL). Sodium tert-butoxide (96 mg, 1 mmol) was added in one portion. After 1.5 h, the reaction was poured into H2O (25 mL) and extracted with EtOAc (3×30 mL). The organics were washed with brine (1×100 mL), dried over MgSO4, filtered and concentrated in vacuo. The tan solid was purified via flash column chromatography (30% EtOAc/hexanes) to provide tert-butyl 5-(2-bromo-4-cyanophenylamino)-3-formylpyrazolo[1,5-a]pyrimidin-7-yl(cyclopropyl)carbamate (106 mg, 32%) as a pale yellow solid. LCMS (ES): >90% pure, m/z 497 [M+1]+.

Workup

  1. extractionextracted with EtOAc (3×30 mL)
  2. washThe organics were washed with brine (1×100 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe tan solid was purified via flash column chromatography (30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-85d20464990d408ca4280f54818a38fb
Source dataset
uspto-grants-2016_04
Patent number
US09303033B2

Reaction notes

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