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

HRID 470174Notes

Reaction equation

HRID 470174 reaction equation
C([O:4][C@@H:5]1[CH2:9][C@@H:8]([N:10]2[C:18]3[C:17]([F:19])=[CH:16][N:15]=[C:14](F)[C:13]=3[N:12]=[CH:11]2)[CH:7]=[CH:6]1)(=O)C.C([O:24][C@@H:25]1[CH2:29][C@@H:28]([N:30]2[C:34]3[C:35](F)=[N:36][CH:37]=[C:38]([F:39])[C:33]=3[N:32]=[CH:31]2)[CH:27]=[CH:26]1)(=O)C>N>[NH2:30][C:14]1[C:13]2[N:12]=[CH:11][N:10]([C@@H:8]3[CH2:9][C@@H:5]([OH:4])[CH:6]=[CH:7]3)[C:18]=2[C:17]([F:19])=[CH:16][N:15]=1.[NH2:10][C:35]1[C:34]2[N:30]([C@@H:28]3[CH2:29][C@@H:25]([OH:24])[CH:26]=[CH:27]3)[CH:31]=[N:32][C:33]=2[C:38]([F:39])=[CH:37][N:36]=1

Participants

5

Reactant 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

Product 2

HCID 58329269(1R,4R)-4-(4-amino-7-fluoro-3H-imidazo[4,5-c]pyridin-3-yl)cyclopent-2-enolHCID 58329291(1R,4R)-4-(4-amino-7-fluoro-1H-imidazo[4,5-c]pyridin-1-yl)cyclopent-2-enol

Reagents, catalysts & solvents 1

HCID 222AmmoniaSolvent

Conditions

Temperature
100 °C

Procedure

Liquid ammonia (150 mL) was added to a mixture of (1R,4R)-4-(4,7-difluoro-1H-imidazo[4,5-c]pyridin-1-yl)cyclopent-2-enyl acetate (4-1) (312 mg, 1.1 mmol, 1 equiv) and (1R,4R)-4-(4,7-difluoro-3H-imidazo[4,5-c]pyridin-3-yl)cyclopent-2-enyl acetate (4-2) (408 mg, 1.5 mmol, 1 equiv). The resulting solution was heated in a high pressure vessel to 100° C. for 2 days. The mixture was then concentrated and purified via reverse phase chromatography (5-95% CH3CN/water with 0.1% TFA modifier) to yield (1R,4R)-4-(4-amino-7-fluoro-1H-imidazo[4,5-c]pyridin-1-yl)cyclopent-2-enol (4-3) as a white solid and (1R,4R)-4-(4-amino-7-fluoro-3H-imidazo[4,5-c]pyridin-3-yl)cyclopent-2-enol (4-4) as a white solid. 1H NMR (4-3) (500 MHz, CD3 OD): δ 8.03 (s, 1H); 7.61 (d, J=3.5 Hz, 1H); 6.31 (m, 1H); 6.20 (m, 1H); 5.93 (m, 1H); 5.09 (m, 1H); 2.40-2.50 (m, 1H); 2.27-2.37 (m, 1H). LRMS m/z (M+H) 235.0 found, 235.1 required. 1H NMR (4-4) (500 MHz, CD3 OD): δ 8.12 (s, 1H); 7.64 (d, J=2.5 Hz, 1H); 6.37 (m, 1H); 6.27 (m, 1H); 6.11 (m, 1H); 4.92 (m, 1H); 2.40-2.50 (m, 1H); 2.27-2.37 (m, 1H). LRMS m/z (M+H) 235.0 found, 235.1 required.

Workup

  1. concentrationThe mixture was then concentrated
  2. custompurified via reverse phase chromatography (5-95% CH3CN/water with 0.1% TFA modifier)

Sources & evidence

ORD record
ord-68da9f02a1af4038ae295625a155e8e0
Source dataset
uspto-grants-2014_01
Patent number
US08629275B2

Reaction notes

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