Butylamine → HCID 178448856, compound

HRID 920660Notes

Reaction equation

HRID 920660 reaction equation
Br[C:2]1[C:10]2[CH:9]=[N:8][C:7](Cl)=[N:6][C:5]=2[N:4]([C@H:12]2[CH2:17][CH2:16][C@H:15]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[CH2:14][CH2:13]2)[CH:3]=1.[CH2:26]([NH2:30])[CH2:27][CH2:28][CH3:29].C([O-])([O-])=O.[K+].[K+].[F:37][C:38]1[CH:43]=[CH:42][C:41](B(O)O)=[CH:40][CH:39]=1>C(O)(C)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH2:26]([NH:30][C:7]1[N:8]=[CH:9][C:10]2[C:2]([C:41]3[CH:42]=[CH:43][C:38]([F:37])=[CH:39][CH:40]=3)=[CH:3][N:4]([C@H:12]3[CH2:13][CH2:14][C@H:15]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:20])[CH3:21])[CH2:16][CH2:17]3)[C:5]=2[N:6]=1)[CH2:27][CH2:28][CH3:29]

Participants

8

Reactant 4

HCID 8007ButylamineHCID 11430Potassium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 178455326HCID 178455326, compound

Product 1

HCID 178448856HCID 178448856, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 5-bromo-7-(trans-4-(tert-butyldimethylsilyloxy)cyclohexyl)-2-chloro-7H-pyrrolo[2,3-d]pyrimidine (0.082 g, 0.18 mmol) in isopropyl alcohol (2.0 mL) was added n-butylamine (0.033 g, 0.45 mmol) in a microwave tube. The resulting mixture was heated under microwave irradiation at 150° C. for 1.5 h. After the reaction cooled to room temperature, the solvent and excess amine was evaporated under vacuum. The residue was dissolved in THF and concentrated under vacuum (3×). Then it was dissolved in THF (2.0 mL) in a microwave tube. To this solution was added K2CO3 (0.050 g, 0.36 mmol), Pd(PPh3)4 (0.021 g, 0.018 mmol), (4-fluorophenyl)boronic acid (0.038 g, 0.27 mmol), and H2O (0.5 mL). The resulting mixture was heated under microwave irradiation at 150° C. for 10 min. After cooled to room temperature, it was washed with brine and extracted with EtOAc (5×). The combined organic layer was dried (Na2SO4) and concentrated. The residue was filtered through a short column of silica gel to provide N-butyl-7-(trans-4-((tert-butyldimethylsilyl)oxy)cyclohexyl)-5-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine which was used for next step without further purification.

Workup

  1. temperatureAfter the reaction cooled to room temperature
  2. customthe solvent and excess amine was evaporated under vacuum
  3. dissolutionThe residue was dissolved in THF
  4. concentrationconcentrated under vacuum (3×)
  5. dissolutionThen it was dissolved in THF (2.0 mL) in a microwave tube
  6. temperatureThe resulting mixture was heated under microwave irradiation at 150° C. for 10 min
  7. temperatureAfter cooled to room temperature
  8. washit was washed with brine
  9. extractionextracted with EtOAc (5×)
  10. dry with materialThe combined organic layer was dried (Na2SO4)
  11. concentrationconcentrated
  12. filtrationThe residue was filtered through a short column of silica gel

Sources & evidence

ORD record
ord-ceb3bb30a7b44cf689669308f6e3330f
Source dataset
uspto-grants-2016_03
Patent number
US09273056B2

Reaction notes

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