Triphenylphosphine → (1R,4R)-4-(4,7-difluoro-3H-imidazo[4,5-c]pyridin-3-yl)cyclopent-2-enyl acetate

HRID 470173

Reaction equation

HRID 470173 reaction equation
[CH3:1][C:2]([O:4][C@H:5]1[CH:9]=[CH:8][C@@H:7](O)[CH2:6]1)=[O:3].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:30][C:31]1[C:36]2[N:37]=[CH:38][NH:39][C:35]=2[C:34]([F:40])=[CH:33][N:32]=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[C:2]([O:4][C@@H:5]1[CH2:6][C@@H:7]([N:39]2[C:35]3[C:34]([F:40])=[CH:33][N:32]=[C:31]([F:30])[C:36]=3[N:37]=[CH:38]2)[CH:8]=[CH:9]1)(=[O:3])[CH3:1].[C:2]([O:4][C@@H:5]1[CH2:6][C@@H:7]([N:37]2[C:36]3[C:31]([F:30])=[N:32][CH:33]=[C:34]([F:40])[C:35]=3[N:39]=[CH:38]2)[CH:8]=[CH:9]1)(=[O:3])[CH3:1]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 10154103rac-(1R,4S)-4-hydroxycyclopent-2-en-1-yl acetateHCID 178506010HCID 178506010, compound

Product 2

HCID 58329299(1R,4R)-4-(4,7-difluoro-3H-imidazo[4,5-c]pyridin-3-yl)cyclopent-2-enyl acetateHCID 58329303(1R,4R)-4-(4,7-difluoro-1H-imidazo[4,5-c]pyridin-1-yl)cyclopent-2-enyl acetate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

(1R,3S)-(+)-cis-4-cyclopentene-1,3-diol 1-acetate (3-1) (500 mg, 3.5 mmol, 1.0 equiv) was dissolved in dry THF (17.6 mL). Triphenylphosphine (1.4 g, 5.3 mmol, 1.5 equiv) was added, followed by 4,7-difluoro-1H-imidazo[4,5-c]pyridine (1-4) (655 mg, 4.2 mmol, 1.2 equiv). The mixture was cooled to 0° C. and DIAD (1 mL, 5.3 mmol, 1.5 equiv) was added dropwise. The resulting mixture was stirred at ambient temperature for 1 hour. Upon disappearance of starting material, the solvent was removed at reduced pressure and the yellow residue was purified via flash chromatography on a 120 g silica gel column (gradient elution 0 to 100% ethyl acetate in hexanes) to yield (1R,4R)-4-(4,7-difluoro-1H-imidazo[4,5-c]pyridin-1-yl)cyclopent-2-enyl acetate (4-1) and (1R,4R)-4-(4,7-difluoro-3H-imidazo[4,5-c]pyridin-3-yl)cyclopent-2-enyl acetate (4-2) as a 2:3 regioisomeric mixture. 1H NMR (4-1) (500 MHz, CDCl3): δ 7.907 (s, 1H); 7.83 (t, J=2.5 Hz, 1H); 6.44 (m, 1H); 6.31 (m, 1H); 5.93-5.99 (m, 2H); 2.67 (m, 1H); 2.43 (m, 1H); 2.10 (s, 3H). LRMS m/z (M+H) 279.9 found, 280.1 required. 1H NMR (4-2) (500 MHz, CDCl3): δ 7.98 (s, 1H); 7.81 (t, J=2 Hz, 1H); 6.44 (m, 1H); 6.31 (m, 1H); 5.93-5.99 (m, 2H); 2.67 (m, 1H); 2.43 (m, 1H); 2.10 (s, 3H). LRMS m/z (M+H) 279.9 found, 280.1 required.

Workup

  1. customUpon disappearance of starting material, the solvent was removed at reduced pressure
  2. customthe yellow residue was purified via flash chromatography on a 120 g silica gel column (gradient elution 0 to 100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-835022cc29d84e90b97eb07a731a43a6
Source dataset
uspto-grants-2014_01
Patent number
US08629275B2

Linked notes

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