3-Chloro-4-fluoroaniline → HCID 58314336, compound

HRID 624697Notes

Reaction equation

HRID 624697 reaction equation
Cl[C:2]1[CH:7]=[C:6]([N:8]([CH2:16][CH:17]2[CH2:19][CH2:18]2)C(=O)OC(C)(C)C)[N:5]2[N:20]=[CH:21][C:22]([CH:23]=[O:24])=[C:4]2[N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl:77][C:78]1[CH:79]=[C:80]([CH:82]=[CH:83][C:84]=1[F:85])[NH2:81]>O1CCOCC1.O>[Cl:77][C:78]1[CH:79]=[C:80]([NH:81][C:2]2[CH:7]=[C:6]([NH:8][CH2:16][CH:17]3[CH2:18][CH2:19]3)[N:5]3[N:20]=[CH:21][C:22]([CH:23]=[O:24])=[C:4]3[N:3]=2)[CH:82]=[CH:83][C:84]=1[F:85]

Participants

7

Reactant 4

HCID 97083-Chloro-4-fluoroanilineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 58196441HCID 58196441, compound

Product 1

HCID 58314336HCID 58314336, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To tert-butyl 5-chloro-3-formylpyrazolo[1,5-a]pyrimidin-7-yl(cyclopropylmethyl)carbamate (50 mg, 0.14 mmol) in 1 mL of 1,4 dioxane was added cesium carbonate (65 mg, 0.2 mmol), Pd (OAc)2 (4 mg, 0.006 mmol), (+)-BINAP (5 mg, 0.009 mmol), 3-chloro-4-fluoroaniline (31 mg, 0.21 mmol). The reaction mixture was heated in microwave at 110° C. for 20 minutes. The mixture was then cooled to room temperature, water was added, and the product was extracted with ether. The organic layer was then concentrated under reduced pressure and the crude product was dissolved in 1:1 mixture of dichloromethane and trifluoroacetic acid at room temperature for 1 hour. The reaction mixture was concentrated with 10 mL of dichloromethane. To the reaction mixture, ether/hexanes (1:1) was added and the flask was sonicated for 10 minutes then filtered to obtain the yellow precipitate. The precipitate was washed with hexane to yield 5-(3-chloro-4-fluorophenylamino)-7-(cyclopropylmethylamino)pyrazolo[1,5-a]pyrimidine-3-carbaldehyde. LCMS (M+1=460)

Workup

  1. temperatureThe mixture was then cooled to room temperature
  2. extractionthe product was extracted with ether
  3. concentrationThe organic layer was then concentrated under reduced pressure
  4. dissolutionthe crude product was dissolved in 1:1 mixture of dichloromethane and trifluoroacetic acid at room temperature for 1 hour
  5. concentrationThe reaction mixture was concentrated with 10 mL of dichloromethane
  6. additionTo the reaction mixture, ether/hexanes (1:1) was added
  7. customthe flask was sonicated for 10 minutes
  8. filtrationthen filtered
  9. customto obtain the yellow precipitate
  10. washThe precipitate was washed with hexane

Sources & evidence

ORD record
ord-3c0377d5f48740dabaf71eb1129a1e1d
Source dataset
uspto-grants-2016_04
Patent number
US09303033B2

Reaction notes

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