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

HRID 470166Notes

Reaction equation

HRID 470166 reaction equation
[CH3:1][C:2]1([CH3:21])[O:6][C@@H:5]2[CH2:7][CH2:8][C@@H:9]([N:10]3[C:18]4[C:17]([F:19])=[CH:16][N:15]=[C:14](F)[C:13]=4[N:12]=[CH:11]3)[C@@H:4]2[O:3]1.CC1(C)O[C@@H]2CC[C@@H]([N:31]3C4C(F)=NC=C(F)C=4N=C3)[C@@H]2O1>N>[CH3:1][C:2]1([CH3:21])[O:6][C@@H:5]2[CH2:7][CH2:8][C@@H:9]([N:10]3[C:18]4[C:17]([F:19])=[CH:16][N:15]=[C:14]([NH2:31])[C:13]=4[N:12]=[CH:11]3)[C@@H:4]2[O:3]1

Participants

4

Reactant 2

HCID 583292721-[(3aS,4R,6aR)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-4,7-difluoro-1H-imidazo[4,5-c]pyridineHCID 583292953-((3aS,4R,6aR)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-4,7-difluoro-3H-imidazo[4,5-c]pyridine

Product 1

HCID 672306201-[(3aS,4R,6aR)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-7-fluoro-1H-imidazo[4,5-c]pyridin-4-amine

Reagents, catalysts & solvents 1

HCID 222AmmoniaSolvent

Conditions

Temperature
85 °C

Procedure

Liquid ammonia (200 mL) was added to a mixture of 1-[(3aS,4R,6aR)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-4,7-difluoro-1H-imidazo[4,5-c]pyridine (1-6) (2.4 g, 8.1 mmol, 1 equiv) and 3-[(3aS,4R,6aR)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-4,7-difluoro-3H-imidazo[4,5-c]pyridine (1-5) (2.5 g, 8.5 mmol, 1 equiv). The resulting solution was heated in a high pressure vessel to 85° C. for 5 days. The mixture was then concentrated and purified via flash chromatography on a 120 g silica gel column (gradient elution 0 to 100% ethyl acetate in dichloromethane and then 100% methanol to elute 1-7) to yield 1-[(3aS,4R,6aR)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-7-fluoro-1H-imidazo[4,5-c]pyridin-4-amine (1-7) as a tan solid in addition to 3-[(3aS,4R,6aR)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-7-fluoro-3H-imidazo[4,5-c]pyridin-4-amine (1-8) and recovered starting material 1-5. 1H NMR (1-7) (500 MHz, CD3 OD): δ 8.13 (s, 1H); 7.62 (d, J=3.7 Hz, 1H); 4.95-4.87 (m, 3H); 2.52-2.42 (m, 1H); 2.21-1.99 (m, 3H); 1.50 (s, 3H); 1.33 (s, 3H). LRMS m/z (M+H) 293.0 found, 293.1 required. 1H NMR (1-8) (500 MHz, CDCl3): δ 7.86-7.81 (m, 1H); 7.76-7.73 (m, 1H); 5.07 (s, 1H); 5.01 (s, 2H); 4.87 (t, J=4.6 Hz, 1H); 4.62 (d, J=6.2 Hz, 1H); 2.66-2.57 (m, 1H); 2.46-2.38 (m, 1H); 2.24-2.17 (m, 2H); 1.57 (s, 3H); 1.35-1.30 (m, 3H). LRMS m/z (M+H) 293.0 found, 293.1 required.

Workup

  1. concentrationThe mixture was then concentrated
  2. custompurified via flash chromatography on a 120 g silica gel column (
  3. washgradient elution 0 to 100% ethyl acetate in dichloromethane
  4. wash100% methanol to elute 1-7)

Sources & evidence

ORD record
ord-0a10fc13fdd542fb92511323720e8de5
Source dataset
uspto-grants-2014_01
Patent number
US08629275B2

Reaction notes

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