Boron tribromide → 4-(4-chlorophenyl)-1-cyclopropyl-5-(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-3-(hydroxymethyl)-4,5-dihydropyrrolo-[3,4-c]pyrazol-6(1H)-one

HRID 873994Notes

Reaction equation

HRID 873994 reaction equation
B(Br)(Br)Br.[Cl:5][C:6]1[CH:11]=[CH:10][C:9]([CH:12]2[C:19]3[C:18]([CH2:20][O:21]C)=[N:17][N:16]([CH:23]4[CH2:25][CH2:24]4)[C:15]=3[C:14](=[O:26])[N:13]2[C:27]2[CH:28]=[C:29]([CH3:37])[C:30]3[N:31]([C:33]([CH3:36])=[N:34][N:35]=3)[CH:32]=2)=[CH:8][CH:7]=1>C(Cl)Cl>[Cl:5][C:6]1[CH:7]=[CH:8][C:9]([CH:12]2[C:19]3[C:18]([CH2:20][OH:21])=[N:17][N:16]([CH:23]4[CH2:24][CH2:25]4)[C:15]=3[C:14](=[O:26])[N:13]2[C:27]2[CH:28]=[C:29]([CH3:37])[C:30]3[N:31]([C:33]([CH3:36])=[N:34][N:35]=3)[CH:32]=2)=[CH:10][CH:11]=1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 918263314-(4-chlorophenyl)-1-cyclopropyl-5-(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-3-(methoxymethyl)-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one

Product 1

HCID 918263324-(4-chlorophenyl)-1-cyclopropyl-5-(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-3-(hydroxymethyl)-4,5-dihydropyrrolo-[3,4-c]pyrazol-6(1H)-oneYield 22.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

BBr3 (1 M in CH2Cl2, 0.337 mL, 0.337 mmol) was added to a solution of 4-(4-chlorophenyl)-1-cyclopropyl-5-(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-3-(methoxymethyl)-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one (130 mg, 0.281 mmol) (Example 130) in CH2Cl2 (5 mL), under an argon atmosphere. The reaction mixture was stirred for 1 h at rt, quenched with brine (100 mL), and extracted with EtOAc (2×100 mL). The combined organic layers were washed with brine (100 mL), dried on Na2SO4 and the solvent was evaporated off under reduced pressure. After purification by silica gel column chromatography (CH2Cl2/MeOH 2-8%), the resulting residue was triturated in diethyl ether to provide the title compound (28 mg) as a colorless solid. tR: 0.77 min (LC-MS 2); ESI-MS: 449.1 [M+H]+ (LC-MS 2); Rf=0.29 (CH2Cl2/MeOH 9:1); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.02-1.09 (m, 2H) 1.19-1.28 (m, 2H) 2.42 (s, 3H) 2.61 (s, 3H) 3.80-3.90 (m, 1H) 4.06 (dd, J=12.90, 5.87 Hz, 1H) 4.30 (dd, J=12.90, 4.30 Hz, 1H) 5.10 (dd, J=5.87, 4.30 Hz, 1H) 6.46 (s, 1H) 7.26-7.41 (m, 5H) 8.49 (s, 1H).

Workup

  1. customquenched with brine (100 mL)
  2. extractionextracted with EtOAc (2×100 mL)
  3. washThe combined organic layers were washed with brine (100 mL)
  4. customdried on Na2SO4
  5. customthe solvent was evaporated off under reduced pressure
  6. customAfter purification by silica gel column chromatography (CH2Cl2/MeOH 2-8%)
  7. customthe resulting residue was triturated in diethyl ether

Sources & evidence

ORD record
ord-d0b352e542e148fe813c9a27925143a7
Source dataset
uspto-grants-2015_03
Patent number
US08975417B2

Reaction notes

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