N-methyl-2-pyrrolidone → HCID 178455822, compound

HRID 1969871Notes

Reaction equation

HRID 1969871 reaction equation
Cl[C:2]1[C:3]([C:11]([CH:14]2[CH2:18][CH:17]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=3)[CH2:16][CH:15]2[CH2:29][CH3:30])=[N:12][NH2:13])=[C:4]2[CH:10]=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.CN1C(=O)CCC1.CC(C)([O-])C.[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCOC(C)=O>[CH2:29]([C@H:15]1[CH2:16][C@@H:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=2)[CH2:18][C@@H:14]1[C:11]1[C:3]2=[C:4]3[CH:10]=[CH:9][NH:8][C:5]3=[N:6][CH:7]=[C:2]2[NH:13][N:12]=1)[CH3:30].[CH2:29]([C@@H:15]1[CH2:16][C@H:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=2)[CH2:18][C@H:14]1[C:11]1[C:3]2=[C:4]3[CH:10]=[CH:9][NH:8][C:5]3=[N:6][CH:7]=[C:2]2[NH:13][N:12]=1)[CH3:30]

Participants

7

Reactant 3

HCID 13387N-methyl-2-pyrrolidoneHCID 23676156Sodium t-butoxideHCID 76829303HCID 76829303, compound

Product 2

HCID 178455822HCID 178455822, compoundYield 14.1%HCID 178455823HCID 178455823, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

A microwave reaction vial was charged with 5-chloro-4-((2-ethyl-4-(4-methoxybenzyloxy)cyclopentyl)(hydrazono)methyl)-1H-pyrrolo[2,3-b]pyridine (0.900 g, 2.11 mmol) and NMP (14.1 mL). Sodium tert-butoxide (0.506 g, 5.27 mmol), palladium(II) acetate (0.047 g, 0.211 mmol) and ((R)-1-[(S)-2-(dicyclohexylphosphino)ferrocenyl]ethyl-di-tert-butylphosphine (0.117 g, 0.211 mmol) were added sequentially and the mixture was heated in a microwave at about 150° C. for about 1 h (250 psi maximum pressure, 1 min ramp, 150 max watts). EtOAc (20 mL) was added and the mixture was filtered through a pad of Celite® while washing with EtOAc (20 mL). Water (15 mL) was added and the layers were separated. The aqueous layer was extracted with EtOAc (2×10 mL), the combined organics were washed with water (3×10 mL), brine (5×10 mL), dried over anhydrous MgSO4, filtered and concd under reduced pressure. The residue was purified by silica gel chromatography eluting with a gradient of 40-100% EtOAc in heptane followed by purification using General Procedure AA to give 1-((1S,2S,4R)-2-ethyl-4-(4-methoxybenzyloxy)cyclopentyl)-3,6-dihydropyrazolo[4,3-d]pyrrolo[2,3-b]pyridine or 1-((1R,2R,4S)-2-ethyl-4-(4-methoxybenzyloxy)cyclopentyl)-3,6-dihydropyrazolo[4,3-d]pyrrolo[2,3-b]pyridine (0.065 g, 8%, Table 2, Method 35, Rt=20.0 min, or =positive) and 1-((1S,2S,4R)-2-ethyl-4-(4-methoxybenzyloxy)cyclopentyl)-3,6-dihydropyrazolo[4,3-d]pyrrolo[2,3-b]pyridine or 1-((1R,2R,4S)-2-ethyl-4-(4-methoxybenzyloxy)cyclopentyl)-3,6-dihydropyrazolo[4,3-d]pyrrolo[2,3-b]pyridine (0.058 g, 7%, Table 2, Method 35, Rt=23.4 min, or =negative): LC/MS (Table 1, Method b) Rt=2.26 min; MS m/z: 391 (M+H)+.

Workup

  1. customA microwave reaction
  2. filtrationthe mixture was filtered through a pad of Celite®
  3. washwhile washing with EtOAc (20 mL)
  4. additionWater (15 mL) was added
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted with EtOAc (2×10 mL)
  7. washthe combined organics were washed with water (3×10 mL), brine (5×10 mL)
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. customThe residue was purified by silica gel chromatography
  11. washeluting with a gradient of 40-100% EtOAc in heptane
  12. customfollowed by purification

Sources & evidence

ORD record
ord-05d1878764544ab5bad7d3dd842d13c7
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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