Sodium Hydroxide → HCID 66722603, compound

HRID 505744Notes

Reaction equation

HRID 505744 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:10]2[CH:14]([C:15]3[CH2:19][CH2:18][CH2:17][CH:16]=3)[CH:13]3[CH2:20][O:21][C:22]4[CH:23]=[C:24]([C:28]([O:30]C)=[O:29])[CH:25]=[CH:26][C:27]=4[C:12]3=[N:11]2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].[OH-].[Na+]>CO.O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([N:10]2[CH:14]([C:15]3[CH2:19][CH2:18][CH2:17][CH:16]=3)[CH:13]3[CH2:20][O:21][C:22]4[CH:23]=[C:24]([C:28]([OH:30])=[O:29])[CH:25]=[CH:26][C:27]=4[C:12]3=[N:11]2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 66722699HCID 66722699, compound

Product 1

HCID 66722603HCID 66722603, compoundYield 22%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 2-(3-chloro-4-cyanophenyl)-3-cyclopentenyl-2,3,3a,4-tetrahydrochromeno[4,3-c]pyrazole-7-carboxylate (190 mg, 0.44 mmol) in methanol (2 mL) and tetrahydrofuran (2 mL) was added 1M aqueous sodium hydroxide (2 mL). The solution was stirred for 20 hours at ambient temperature. The resulting slurry was concentrated to half volume and acidified to pH=2 with 1M hydrochloric acid. The resulting solid was collected by vacuum filtration. The solid was treated with hot N,N-dimethylformamide and methanol to provide 2-(3-chloro-4-cyanophenyl)-3-cyclopentenyl-2,3,3a,4-tetrahydrochromeno[4,3-c]pyrazole-7-carboxylic acid (yellow solid, 40 mg, 22% yield). The title compound was largely present as 3RS,3aRS)-2-(3-chloro-4-cyanophenyl)-3-cyclopentenyl-2,3,3a,4-tetrahydrochromeno[4,3-c]pyrazole-7-carboxylic acid. Reversed-phase HPLC on 4.6×50 mm C-18 column, tR=3.05 minutes (10 to 90% acetonitrile/water over 4 minutes at 4 mL/minute with detection 254 nm, at 20° C.); HRMS Calculated for C23H18ClN3O3: 420.1109 (M+H)+. Found: 420.1127; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.59-1.89 (m, 2H), 2.03-2.14 (m, 2H), 2.14-2.23 (m, 2H), 3.89 (dd, J=13.02, 10.34 Hz, 1H), 4.05 (ddd, J=12.89, 10.74, 5.91 Hz, 1H), 4.67 (dd, J=10.34, 5.77 Hz, 1H), 5.51 (d, J=11.01 Hz, 1H), 5.63 (br. s., 1H), 7.00 (br. s., 1H) 7.29 (br. s., 1H), 7.43 (d, J=1.61 Hz, 1H), 7.56 (dd, J=8.19, 1.48 Hz, 1H), 7.71 (d, J=8.59 Hz, 1H), 7.94 (d, J=8.06 Hz, 1H), 13.16 (br. s., 1H).

Workup

  1. concentrationThe resulting slurry was concentrated to half volume
  2. filtrationThe resulting solid was collected by vacuum filtration
  3. additionThe solid was treated with hot N,N-dimethylformamide and methanol

Sources & evidence

ORD record
ord-f9864687a2e043eaa1dda24b28c7f7b4
Source dataset
uspto-grants-2010_08
Patent number
US07781428B2

Reaction notes

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