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

HRID 470169Notes

Reaction equation

HRID 470169 reaction equation
[CH3:1][C:2]1([CH3:21])[O:6][C@@H:5]2[CH:7]=[CH: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]2C=C[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[CH:7]=[CH: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 583292881-[(3aS,4R,6aR)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-4,7-difluoro-1H-imidazo[4,5-c]pyridineHCID 583293123-[(3aS,4R,6aR)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-4,7-difluoro-3H-imidazo[4,5-c]pyridine

Product 1

HCID 672351381-[(3aS,4R,6aR)-2,2-dimethyl-4,6a-dihydro-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 (30 mL) was added to a mixture of 1-[(3aS,4R,6aR)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-4,7-difluoro-1H-imidazo[4,5-c]pyridine (2-2) (160 mg, 0.55 mmol, 1 equiv) and 3-[(3aS,4R,6aR)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-4,7-difluoro-3H-imidazo[4,5-c]pyridine (2-1) (160 mg, 0.55 mmol, 1 equiv). The resulting solution was heated in a high pressure vessel to 85° C. for 4 days. The mixture was then concentrated and purified via flash chromatography on a 40 g silica gel column (gradient elution 0 to 100% ethyl acetate in dichloromethane and then 100% methanol to elute 2-3) to yield 1-[(3aS,4R,6aR)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-7-fluoro-1H-imidazo[4,5-c]pyridin-4-amine (2-3) as a light yellow solid in addition to 3-[(3aS,4R,6aR)-2,2-dimethyl-4,6a-dihydro-3 aH-cyclopenta[d][1,3]dioxol-4-yl]-7-fluoro-3H-imidazo[4,5-c]pyridin-4-amine (2-4) and recovered starting material 2-2. 1H NMR (2-3) (500 MHz, CDCl3): δ 7.76 (d, J=3.0 Hz, 1H); 7.63 (s, 1H); 6.36 (d, J=5.7 Hz, 1H); 6.03 (d, J=5.7 Hz, 1H); 5.68 (s, 1H); 5.42 (d, J=5.6 Hz, 1H); 5.03 (s, 2H); 4.68 (d, J=5.7 Hz, 1H); 1.50 (t, J=9.7 Hz, 3H); 1.42-1.33 (m, 3H). LRMS m/z (M+H) 291.0 found, 291.1 required. 1H NMR (2-4) (500 MHz, CDCl3): δ 7.77 (d, J=2.3 Hz, 1H); 7.73 (s, 1H); 6.47-6.43 (m, 1H); 6.17-6.14 (m, 1H); 5.87 (s, 1H); 5.41 (d, J=6.0 Hz, 1H); 5.00 (s, 2H); 4.69 (d, J=6.1 Hz, 1H); 1.55 (s, 3H); 1.38 (s, 3H). LRMS m/z (M+H) 291.0 found, 291.1 required.

Workup

  1. concentrationThe mixture was then concentrated
  2. custompurified via flash chromatography on a 40 g silica gel column (
  3. washgradient elution 0 to 100% ethyl acetate in dichloromethane
  4. wash100% methanol to elute 2-3)

Sources & evidence

ORD record
ord-7efc884f4c0b452b88d806c8408db363
Source dataset
uspto-grants-2014_01
Patent number
US08629275B2

Reaction notes

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