Pyrrolidine → HCID 58396775, compound

HRID 1361681Notes

Reaction equation

HRID 1361681 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 purifed 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. extractiondesalted by aqueous NaHCO3/EtOAc extraction
  10. custompurified by flash chromatography (2:1 to 1:1 hexanes/EtOAc
  11. customThe resulting solid was triturated with a small amount of t-BuOMe
  12. customto provide the product

Sources & evidence

ORD record
ord-fd842771b5214ab0935e505314b53790
Source dataset
uspto-grants-2011_02
Patent number
US07880000B2

Reaction notes

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