Pyrrolidine → HCID 57756225, compound

HRID 911153Notes

Reaction equation

HRID 911153 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[C:9]([O:14][C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22]4[C:31]5[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=5)[C:25]([C:32]5[CH:39]=[CH:38][C:35]([CH:36]=O)=[CH:34][CH:33]=5)=[N:24][N:23]=4)=[CH:17][CH:16]=3)=[N:10][CH:11]=[CH:12][CH:13]=2)[CH:5]=[CH:4][N:3]=1.[NH:40]1[CH2:44][CH2:43][CH2:42][CH2:41]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>CC(O)=O.CO>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[C:9]([O:14][C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22]4[C:31]5[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=5)[C:25]([C:32]5[CH:33]=[CH:34][C:35]([CH2:36][N:40]6[CH2:44][CH2:43][CH2:42][CH2:41]6)=[CH:38][CH:39]=5)=[N:24][N:23]=4)=[CH:17][CH:16]=3)=[N:10][CH:11]=[CH:12][CH:13]=2)[CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 31268PyrrolidineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 86614167HCID 86614167, compound

Product 1

HCID 57756225HCID 57756225, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

A 25 mL RBF under nitrogen was charged with 4-(4-(4-(3-(2-aminopyrimidin-4-yl)pyridin-2-yloxy)phenylamino)phthalazin-1-yl)benzaldehyde (90 mg, 0.18 mmol), pyrrolidine (125 mg, 1.8 mmol) and MeOH (3.5 mL, 0.05 M). HOAc was added (0.02 mL, 0.36 mmol) and the reaction mixture was stirred at RT for 2 hrs. The reaction mixture was cooled to 0° C. and sodium triacetoxyborohydride (186 mg, 0.90 mmol) was added portionwise. The mixture was stirred at RT overnight, then cooled to 0° C. and basified with aqueous sodium bicarbonate and the product was extracted into DCM. The organic layers were collected, dried over sodium sulfate, filtered and concentrated to give brown residue. The crude residue was purified by Gilson reverse phase liquid chromatography (5%-85% CH3CN/H2O+0.1% TFA). Product-containing fractions were combined and basified with aqueous sodium bicarbonate. This was extracted with EtOAc, dried over sodium sulfate, filtered, concentrated under reduced pressure, and dried under high vacuum to afford N-(4-(3-(2-aminopyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4-(4-(pyrrolidin-1-ylmethyl)phenyl)phthalazin-1-amine as a light yellow solid. MS m/z=567 [M+H]+. Calc'd for C34H30N8O: 566.7.

Workup

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. stirringThe mixture was stirred at RT overnight
  3. extractionthe product was extracted into DCM
  4. customThe organic layers were collected
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give brown residue
  9. customThe crude residue was purified by Gilson reverse phase liquid chromatography (5%-85% CH3CN/H2O+0.1% TFA)
  10. extractionThis was extracted with EtOAc
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customdried under high vacuum

Sources & evidence

ORD record
ord-31f60496dcd741dd8d1a6fb7a4e6a17a
Source dataset
uspto-grants-2011_09
Patent number
US08022221B2

Reaction notes

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