Hydrochloric Acid → HCID 66719463, compound

HRID 2390453Notes

Reaction equation

HRID 2390453 reaction equation
[O:1]1[CH2:3][C@H:2]1[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([N:14]3[CH:19]=[CH:18][C:17]([C:20]4[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=4)=[CH:16][C:15]3=[O:30])=[CH:11][CH:12]=2)[CH:7]=[N:6]1.[NH:31]1[CH2:35][CH2:34][CH2:33][CH2:32]1.[ClH:36]>O1CCCC1.ClCCl>[ClH:36].[OH:1][C@@H:2]([CH2:3][N:31]1[CH2:35][CH2:34][CH2:33][CH2:32]1)[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([N:14]3[CH:19]=[CH:18][C:17]([C:20]4[CH:25]=[CH:24][C:23]([C:26]([F:27])([F:28])[F:29])=[CH:22][CH:21]=4)=[CH:16][C:15]3=[O:30])=[CH:11][CH:12]=2)[CH:7]=[N:6]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 31268PyrrolidineHCID 57625502HCID 57625502, compound

Product 1

HCID 66719463HCID 66719463, compoundYield 87.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

To (R)-1-(1-(oxiran-2-ylmethyl)-1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)-pyridin-2(1H)-one (250 mg, 0.61 mmol) in tetrahydrofuran (5 mL) was added LiClO4 (969 mg, 9.11 mmol) followed by pyrrolidine (0.51 mL, 6.1 mmol). The reaction mixture was heated in a 45° C. oil bath for 3.75 h. The reaction mixture was cooled to ambient temperature, diluted with dichloromethane (50 ml) and washed with water (25 mL), brine (25 mL), dried (Na2SO4), and concentrated under reduced pressure. The material was purified by column chromatography (silica gel, 9:1 CH2Cl2/MeOH to 90:9:1 CH2Cl2/MeOH/conc. NH4OH). The dried residue (233 mg, 0.48 mmol) was dissolved in dichloromethane (2 mL), and HCl (1.25 M solution in methanol, 0.42 mL, 0.53 mmol) was added. The mixture was concentrated under reduced pressure and dried to afford the title compound (240 mg, 76%) as a yellow solid: 1H NMR (500 MHz, DMSO-d6) δ 9.60 (br s, 1H), 8.20 (s, 1H), 8.02-8.00 (m, 2H), 7.89-7.80 (m, 5H), 7.46 (dd, J=8.5, 1.5 Hz, 1H), 6.89 (d, J=2.0 Hz, 1H), 6.74 (dd, J=7.5, 2.0 Hz, 1H), 4.57-4.53 (m, 1H), 4.49-4.46 (m, 1H), 4.27 (br s, 1H), 3.25-2.75 (br m, 6H), 1.85 (br s, 4H); ESI MS m/z 483 [M+H]+; HPLC (Method B)>99% (AUC), tR=15.1 min; [α]23D −11.3° (c 0.11, Methanol).

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. washwashed with water (25 mL), brine (25 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated under reduced pressure
  5. customThe material was purified by column chromatography (silica gel, 9:1 CH2Cl2/MeOH to 90:9:1 CH2Cl2/MeOH/conc. NH4OH)
  6. concentrationThe mixture was concentrated under reduced pressure
  7. customdried

Sources & evidence

ORD record
ord-3e58955d32204025aabea80309350267
Source dataset
uspto-grants-2012_09
Patent number
US08273770B2

Reaction notes

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