Pyrrolidine → HCID 58396775, compound

HRID 446326Notes

Reaction equation

HRID 446326 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C:28]2[CH:33]=[CH:32][N:31]=[C:30]([NH:34][CH3:35])[N:29]=2)[C:5]([O:8][C:9]2[CH:10]=[C:11]([CH:24]=[CH:25][C:26]=2[CH3:27])[C:12]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH:21]([CH3:23])[CH3:22])[CH:16]=2)=[O:13])=[N:6][CH:7]=1.[NH:36]1[CH2:40][CH2:39][CH2:38][CH2:37]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:21]([C:17]1[CH:16]=[C:15]([NH:14][C:12](=[O:13])[C:11]2[CH:24]=[CH:25][C:26]([CH3:27])=[C:9]([O:8][C:5]3[C:4]([C:28]4[CH:33]=[CH:32][N:31]=[C:30]([NH:34][CH3:35])[N:29]=4)=[CH:3][C:2]([N:36]4[CH2:40][CH2:39][CH2:38][CH2:37]4)=[CH:7][N:6]=3)[CH:10]=2)[CH:20]=[CH:19][CH:18]=1)([CH3:23])[CH3:22]

Participants

5

Reactant 3

HCID 31268PyrrolidineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 58588170HCID 58588170, compound

Product 1

HCID 58396775HCID 58396775, compound

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
70 °C

Procedure

The title compound was prepared using the procedure of Harris et. al. [Organic Letters 2002, 4 (17), 2885-2888.]: In a N2-flushed sealing tube, 3-[5-Chloro-3-(2-methylamino-pyrimidin-4-yl)-pyridin-2-yloxy]-N-(3-isopropyl-phenyl)-4-methyl-benzamide (100 mg, 0.21 mmol), pyrrolidine (0.022 mL, 0.26 mmol), Pd2(dba)3 (5.1 mg, 0.0055 mmol), and 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (5.2 mg, 0.13 mmol) were combined. The tube was flushed with argon, and 1 M Li(TMS)2 in THF (Aldrich, 0.67 ml) was added. The sealed tube was heated at 70° C. for 20 h. 1 N HCl was added, the mixture was stirred 5 minutes, then saturated aqueous NaHCO3 was added. After extraction, the organic layer was dried over Na2SO4. After concentration, the residue was purified by HPLC (Gilson, acidic mobile phase), desalted by aqueous NaHCO3/EtOAc extraction, and purified by flash chromatography (2:1 to 1:1 hexanes/EtOAc. The resulting solid was triturated with a small amount of t-BuOMe to provide the product. MS m/z=523 [M+H]+. Calc'd for C31H34N6O2: 522.65.

Workup

  1. customIn a N2-flushed
  2. customThe tube was flushed with argon, and 1 M Li(TMS)2 in THF (Aldrich, 0.67 ml)
  3. additionwas added
  4. addition1 N HCl was added
  5. additionsaturated aqueous NaHCO3 was added
  6. extractionAfter extraction
  7. dry with materialthe organic layer was dried over Na2SO4
  8. concentrationAfter concentration
  9. customthe residue was purified by HPLC (Gilson, acidic mobile phase)
  10. extractiondesalted by aqueous NaHCO3/EtOAc extraction
  11. custompurified by flash chromatography (2:1 to 1:1 hexanes/EtOAc
  12. customThe resulting solid was triturated with a small amount of t-BuOMe
  13. customto provide the product

Sources & evidence

ORD record
ord-f18390e84a984bfc96f8b075d68ad05d
Source dataset
uspto-grants-2013_07
Patent number
US08476434B2

Reaction notes

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