4,7-difluoro-3-((3aS,4S,6aR)-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-3H-imidazo[4,5-c]pyridine → 7-fluoro-1-((3aS,4S,6aR)-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-1H-imidazo[4,5-c]pyridin-4-amine

HRID 470183Notes

Reaction equation

HRID 470183 reaction equation
F[C:2]1[C:7]2[N:8]=[CH:9][N:10]([C@H:11]3[C@H:18]4[C@H:14]([O:15][C:16]([CH3:20])([CH3:19])[O:17]4)[CH:13]=[C:12]3[F:21])[C:6]=2[C:5]([F:22])=[CH:4][N:3]=1.F[C:24]1[C:29]2[N:30]([C@H:33]3[C@H:40]4[C@H:36]([O:37][C:38]([CH3:42])([CH3:41])[O:39]4)[CH:35]=[C:34]3[F:43])[CH:31]=[N:32][C:28]=2[C:27]([F:44])=[CH:26][N:25]=1>N>[F:22][C:5]1[C:6]2[N:10]([C@H:11]3[C@H:18]4[C@H:14]([O:15][C:16]([CH3:19])([CH3:20])[O:17]4)[CH:13]=[C:12]3[F:21])[CH:9]=[N:8][C:7]=2[C:2]([NH2:25])=[N:3][CH:4]=1.[F:44][C:27]1[C:28]2[N:32]=[CH:31][N:30]([C@@H:33]3[C@H:40]4[C@H:36]([O:37][C:38]([CH3:42])([CH3:41])[O:39]4)[CH:35]=[C:34]3[F:43])[C:29]=2[C:24]([NH2:3])=[N:25][CH:26]=1

Participants

5

Reactant 2

HCID 583293054,7-difluoro-3-((3aS,4S,6aR)-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-3H-imidazo[4,5-c]pyridineHCID 583293104,7-difluoro-1-((3aS,4S,6aR)-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-1H-imidazo[4,5-c]pyridine

Product 2

HCID 583293077-fluoro-1-((3aS,4S,6aR)-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-1H-imidazo[4,5-c]pyridin-4-amineHCID 672500587-fluoro-3-((3aS,4R,6aR)-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-3H-imidazo[4,5-c]pyridin-4-amine

Reagents, catalysts & solvents 1

HCID 222AmmoniaSolvent

Conditions

Temperature
100 °C

Procedure

Liquid ammonia (150 mL) was added to a mixture of 4,7-difluoro-1-((3aS,4S,6aR)-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-1H-imidazo[4,5-c]pyridine (5-7) (140 mg, 0.45 mmol, 1 equiv) and 4,7-difluoro-3-((3aS,4S,6aR)-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-3H-imidazo[4,5-c]pyridine (5-8) (160 mg, 0.51 mmol, 1 equiv). The resulting solution was heated in a high pressure vessel to 100° C. for 3 days. The mixture was then concentrated and purified via flash chromatography (40 g SiO2; 20-100% EtOAc in hexanes, holding at 100% EtOAc to elute 5-9) to yield 7-fluoro-1-((3aS,4S,6aR)-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-1H-imidazo[4,5-c]pyridin-4-amine (5-9) as a white solid and 7-fluoro-3-((3aS,4R,6aR)-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-3H-imidazo[4,5-c]pyridin-4-amine (5-10) as a white solid. 1H NMR (5-9) (500 MHz, CDCl3): δ 7.77 (d, J=3.5 Hz, 1H); 7.71 (s, 1H); 5.74 (s, 1H); 5.58 (s, 1H); 5.36 (m, 1H); 5.12 (s, 2H); 4.75 (t, J=5 Hz, 1H); 1.55 (s, 3H); 1.36 (s, 3H). LRMS m/z (M+H) 308.9 found, 309.1 required. LRMS m/z (5-10) (M+H) 308.9 found, 309.1 required.

Workup

  1. concentrationThe mixture was then concentrated
  2. custompurified via flash chromatography (40 g SiO2; 20-100% EtOAc in hexanes, holding at 100% EtOAc to elute 5-9)

Sources & evidence

ORD record
ord-57fd9c7103ce4836960b2d8c057e551c
Source dataset
uspto-grants-2014_01
Patent number
US08629275B2

Reaction notes

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