Hydrochloric Acid → HCID 86724076, compound

HRID 1748727Notes

Reaction equation

HRID 1748727 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[S:15][CH2:14][CH2:13][N:12]([CH2:16][C:17]([O:19]C)=[O:18])[C:11]2[N:21]([CH3:30])[N:22]=[C:23]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=3)[C:10]1=2.[OH-].[Li+].Cl>C1COCC1.O>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[S:15][CH2:14][CH2:13][N:12]([CH2:16][C:17]([OH:19])=[O:18])[C:11]2[N:21]([CH3:30])[N:22]=[C:23]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=3)[C:10]1=2

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 86724075HCID 86724075, compound

Product 1

HCID 86724076HCID 86724076, compoundYield 56.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of methyl 2-[4-(2,4-dichlorophenyl)-1-methyl-3-(2-pyridyl)-6,7-dihydro-4H-pyrazolo[3,4-e][1,4]thiazepin-8-yl]acetate (0.300 g, 0.64 mmol) and lithium hydroxide (0.062 g, 2.6 mmol) in THF (10 mL) and water (5 mL) was stirred at rt for about 2 h. Then 1 M aqueous HCl (15 mL) was added and the mixture was extracted with ethyl acetate (2×25 mL). The combined organic layers were dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by prep-HPLC (Table 2, Method a) to give 2-[4-(2,4-dichlorophenyl)-1-methyl-3-(2-pyridyl)-6,7-dihydro-4H-pyrazolo[3,4-e][1,4]thiazepin-8-yl]acetic acid (0.160 g, 0.36 mmol, 56%) as a white solid: LC-MS (Table 1, Method b) Rt=6.57 min; m/z 449 (M+H)+; 1H-NMR (CDCl3, Bruker 400 MHz) δ 2.73-2.91 (2 H, m) 3.40-3.63 (2 H, m) 3.92 (3 H, s) 4.12 (1 H, d, J=18.4 Hz) 4.21 (1 H, d, J=18.4 Hz) 5.95 (1 H, br s) 6.46 (1 H, s) 6.94 (1 H, d, J=8.4 Hz) 7.00-7.07 (2H, m) 7.40 (1H, d, J=2.1Hz) 7.58 (1H, td, J=7.5, 1.8 Hz) 7.72 (1H, d, J=7.9 Hz) 8.40 (1H, d, J=5.0 Hz).

Workup

  1. extractionthe mixture was extracted with ethyl acetate (2×25 mL)
  2. dry with materialThe combined organic layers were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by prep-HPLC (Table 2, Method a)

Sources & evidence

ORD record
ord-5cbd14a485fe4126aa25213396261286
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

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