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Chemical Structure| 1208081-25-7 Chemical Structure| 1208081-25-7

Structure of 1208081-25-7

Chemical Structure| 1208081-25-7

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Product Details of [ 1208081-25-7 ]

CAS No. :1208081-25-7
Formula : C7H10N2O3
M.W : 170.17
SMILES Code : O=C(C1=CC(CO)=NN1C)OC
English Name :Methyl 3-(hydroxymethyl)-1-methyl-1H-pyrazole-5-carboxylate
MDL No. :MFCD10568327
InChI Key :MZHNDLRCKWKTSU-UHFFFAOYSA-N
Pubchem ID :50998931

Safety of [ 1208081-25-7 ]

Application In Synthesis of [ 1208081-25-7 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 1208081-25-7 ]

[ 1208081-25-7 ] Synthesis Path-Downstream   1~14

  • 1
  • [ 1208081-25-7 ]
  • [ 2460256-20-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: dichloromethane / 0.75 h / 0 °C 2.1: 0.5 h / 70 °C 2.2: 5 h / 70 °C 3.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 16 h / 20 °C 4.1: N-ethyl-N,N-diisopropylamine; propylphosphonic anhydride / ethyl acetate; 2-methyltetrahydrofuran / 18 h / 26 °C
Multi-step reaction with 4 steps 1.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0 °C 2.1: 0.5 h / 70 °C 2.2: 5 h / 70 °C 3.1: lithium hydroxide monohydrate; water / tetrahydrofuran / 16 h / 20 °C 4.1: N-ethyl-N,N-diisopropylamine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / ethyl acetate; 2-methyltetrahydrofuran / 18 h / 26 °C
Multi-step reaction with 4 steps 1: N-ethyl-N,N-diisopropylamine / dichloromethane / 1 h / Inert atmosphere; Cooling with ice 2: 80 min / 20 - 70 °C 3: lithium hydroxide monohydrate; water / tetrahydrofuran / 1 h / 20 °C 4: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 18 h / 20 °C / Inert atmosphere
  • 2
  • [ 1208081-25-7 ]
  • [ 2460256-21-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: dichloromethane / 0.75 h / 0 °C 2.1: 0.5 h / 70 °C 2.2: 5 h / 70 °C 3.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 16 h / 20 °C 4.1: N-ethyl-N,N-diisopropylamine; propylphosphonic anhydride / ethyl acetate; 2-methyltetrahydrofuran / 18 h / 26 °C 5.1: formic acid / 0.5 h / 27 °C 5.2: 1 h / 27 °C
Multi-step reaction with 5 steps 1.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0 °C 2.1: 0.5 h / 70 °C 2.2: 5 h / 70 °C 3.1: lithium hydroxide monohydrate; water / tetrahydrofuran / 16 h / 20 °C 4.1: N-ethyl-N,N-diisopropylamine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / ethyl acetate; 2-methyltetrahydrofuran / 18 h / 26 °C 5.1: formic acid / 0.5 h / 27 °C
Multi-step reaction with 5 steps 1.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 1 h / Inert atmosphere; Cooling with ice 2.1: 80 min / 20 - 70 °C 3.1: lithium hydroxide monohydrate; water / tetrahydrofuran / 1 h / 20 °C 4.1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 18 h / 20 °C / Inert atmosphere 5.1: formic acid / 30 min / 20 °C 5.2: pH >14
  • 3
  • [ 1208081-25-7 ]
  • [ 2460256-22-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: dichloromethane / 0.75 h / 0 °C 2.1: 0.5 h / 70 °C 2.2: 5 h / 70 °C 3.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 16 h / 20 °C 4.1: N-ethyl-N,N-diisopropylamine; 1-propanephosphonic anhydride / ethyl acetate; 2-methyltetrahydrofuran / 18 h / 26 °C 5.1: formic acid / 0.5 h / 27 °C 5.2: 1 h / 27 °C 6.1: dmap; pyridine / tetrahydrofuran; dichloromethane / 18 h / 20 °C
Multi-step reaction with 6 steps 1.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0 °C 2.1: 0.5 h / 70 °C 2.2: 5 h / 70 °C 3.1: lithium hydroxide monohydrate; water / tetrahydrofuran / 16 h / 20 °C 4.1: N-ethyl-N,N-diisopropylamine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / ethyl acetate; 2-methyltetrahydrofuran / 18 h / 26 °C 5.1: formic acid / 0.5 h / 27 °C 6.1: dmap; pyridine / tetrahydrofuran; dichloromethane / 18 h / 20 °C
  • 4
  • [ 1208081-25-7 ]
  • [ 2460256-23-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: dichloromethane / 0.75 h / 0 °C 2.1: 0.5 h / 70 °C 2.2: 5 h / 70 °C 3.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 16 h / 20 °C 4.1: N-ethyl-N,N-diisopropylamine; 1-propanephosphonic anhydride / ethyl acetate; 2-methyltetrahydrofuran / 18 h / 26 °C 5.1: formic acid / 0.5 h / 27 °C 5.2: 1 h / 27 °C 6.1: dmap; pyridine / tetrahydrofuran; dichloromethane / 18 h / 20 °C 7.1: formic acid / 18 h / 70 °C
Multi-step reaction with 7 steps 1.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0 °C 2.1: 0.5 h / 70 °C 2.2: 5 h / 70 °C 3.1: lithium hydroxide monohydrate; water / tetrahydrofuran / 16 h / 20 °C 4.1: N-ethyl-N,N-diisopropylamine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / ethyl acetate; 2-methyltetrahydrofuran / 18 h / 26 °C 5.1: formic acid / 0.5 h / 27 °C 6.1: dmap; pyridine / tetrahydrofuran; dichloromethane / 18 h / 20 °C 7.1: formic acid / 18 h / 70 °C
  • 5
  • [ 1208081-25-7 ]
  • [ 3030228-43-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1.1: dichloromethane / 0.75 h / 0 °C 2.1: 0.5 h / 70 °C 2.2: 5 h / 70 °C 3.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 16 h / 20 °C 4.1: N-ethyl-N,N-diisopropylamine; propylphosphonic anhydride / ethyl acetate; 2-methyltetrahydrofuran / 18 h / 26 °C 5.1: formic acid / 0.5 h / 27 °C 5.2: 1 h / 27 °C 6.1: dmap; pyridine / tetrahydrofuran; dichloromethane / 18 h / 20 °C 7.1: formic acid / 18 h / 70 °C 8.1: tetrahydrofuran / 27 °C
Multi-step reaction with 8 steps 1.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0 °C 2.1: 0.5 h / 70 °C 2.2: 5 h / 70 °C 3.1: lithium hydroxide monohydrate; water / tetrahydrofuran / 16 h / 20 °C 4.1: N-ethyl-N,N-diisopropylamine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / ethyl acetate; 2-methyltetrahydrofuran / 18 h / 26 °C 5.1: formic acid / 0.5 h / 27 °C 6.1: dmap; pyridine / tetrahydrofuran; dichloromethane / 18 h / 20 °C 7.1: formic acid / 18 h / 70 °C 8.1: tetrahydrofuran / 6 h / 27 °C
  • 6
  • [ 1208081-25-7 ]
  • [ 2460249-20-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1.1: dichloromethane / 0.75 h / 0 °C 2.1: 0.5 h / 70 °C 2.2: 5 h / 70 °C 3.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 16 h / 20 °C 4.1: N-ethyl-N,N-diisopropylamine; 1-propanephosphonic anhydride / ethyl acetate; 2-methyltetrahydrofuran / 18 h / 26 °C 5.1: formic acid / 0.5 h / 27 °C 5.2: 1 h / 27 °C 6.1: dmap; pyridine / tetrahydrofuran; dichloromethane / 18 h / 20 °C 7.1: formic acid / 18 h / 70 °C 8.1: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 18 h / 30 °C
  • 7
  • [ 1208081-25-7 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: dichloromethane / 0.75 h / 0 °C 2.1: 0.5 h / 70 °C 2.2: 5 h / 70 °C 3.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 16 h / 20 °C
Multi-step reaction with 3 steps 1.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0 °C 2.1: 0.5 h / 70 °C 2.2: 5 h / 70 °C 3.1: lithium hydroxide monohydrate; water / tetrahydrofuran / 16 h / 20 °C
Multi-step reaction with 2 steps 1: silver(l) oxide / N,N-dimethyl-formamide / 20 °C 2: lithium hydroxide; water / tetrahydrofuran / 20 °C
  • 8
  • [ 1208081-25-7 ]
  • [ 2122011-13-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: dichloromethane / 0.75 h / 0 °C 2.1: 0.5 h / 70 °C 2.2: 5 h / 70 °C
Multi-step reaction with 2 steps 1.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0 °C 2.1: 0.5 h / 70 °C 2.2: 5 h / 70 °C
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / dichloromethane / 1 h / Inert atmosphere; Cooling with ice 2: 80 min / 20 - 70 °C
  • 9
  • [ 1208081-25-7 ]
  • [ 124-63-0 ]
  • [ 2460255-85-8 ]
YieldReaction ConditionsOperation in experiment
99% In dichloromethane at 0℃; for 0.75h; Intermediate 5: Lithium 3-(methoxymethyl)-1-methyl-1H-pyrazole-5-carboxylate A solution of methanesulfonyl chloride (11.32 g, 98.8 mmol) in dichloromethane (50 mL) was added dropwise to a cooled (0° C.) mixture of methyl 3-(hydroxymethyl)-1-methyl-1H-pyrazole-5-carboxylate (CAS No.1208081-25-7, 15.0 g, 88.1 mmol) and diisopropylethyl amine (14.8 g, 115 mmol) in dichloromethane (250 mL). The mixture was stirred at 0° C. for 45 minutes after the addition was complete. The reaction mixture was washed with sat. aq NH4Cl, and the organic layer dried over sodium sulfate, filtered, and concentrated to give methyl 1-methyl-3-[(methylsulfonyl)oxy]methyl}-1H-pyrazole-5-carboxylate (5a, 22.6 g, >99%) as a yellow oil, which was used without further purification. 1H NMR (400 MHz, CHLOROFORM-d) δ=6.98 (s, 1H), 5.26 (s, 2H), 4.20 (s, 3H), 3.91 (s, 3H), 3.03 (s, 3H).
99% With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; 4.2 2. Preparation of Intermediate 5: Lithium 3-(methoxymethyl)-1-methyl-1H- pyrazole-5-carboxylate. A solution of methanesulfonyl chloride (11.32 g, 98.8 mmol) in dichloromethane (50 mL) was added dropwise to a cooled (0 °C) mixture of methyl 3-(hydroxymethyl)-1- methyl-1H-pyrazole-5-carboxylate (CAS 1208081-25-7, 15.0 g, 88.1 mmol) and diisopropylethyl amine (14.8 g, 115 mmol) in dichloromethane (250 mL). The mixture was stirred at 0 °C for 45 minutes after the addition was complete. The reaction mixture was washed with sat. aq NH4Cl, and the organic layer dried over sodium sulfate, filtered, and concentrated to give methyl 1-methyl-3-[(methylsulfonyl)oxy]methyl}-1H-pyrazole-5- carboxylate (5a, 22.6 g, >99%) as a yellow oil, which was used without further purification.1H NMR (400 MHz, CHLOROFORM-d) δ = 6.98 (s, 1H), 5.26 (s, 2H), 4.20 (s, 3H), 3.91 (s, 3H), 3.03 (s, 3H).
99% With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; 1 Preparation of Intermediate 5: Lithium 3-(methoxymethyl)-1-methyl-1H-pyrazole- 5-carboxylate. A solution of methanesulfonyl chloride (11.32 g, 98.8 mmol) in dichloromethane (50 mL) was added dropwise to a cooled (0 °C) mixture of methyl 3-(hydroxymethyl)-1- methyl-1H-pyrazole-5-carboxylate (CAS 1208081-25-7, 15.0 g, 88.1 mmol) and diisopropylethyl amine (14.8 g, 115 mmol) in dichloromethane (250 mL). The mixture was stirred at 0 °C for 45 minutes after the addition was complete. The reaction mixture was washed with sat. aq NH4Cl, and the organic layer dried over sodium sulfate, filtered, and concentrated to give methyl 1-methyl-3-[(methylsulfonyl)oxy]methyl}-1H-pyrazole-5- carboxylate (5a, 22.6 g, >99%) as a yellow oil, which was used without further purification.1H NMR (400 MHz, CHLOROFORM-d) δ = 6.98 (s, 1H), 5.26 (s, 2H), 4.20 (s, 3H), 3.91 (s, 3H), 3.03 (s, 3H).
99% With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; 4.2 2. Preparation of Intermediate 5: Lithium 3-(methoxymethyl)-1-methyl-1H- pyrazole-5-carboxylate. A solution of methanesulfonyl chloride (11.32 g, 98.8 mmol) in dichloromethane (50 mL) was added dropwise to a cooled (0 °C) mixture of methyl 3-(hydroxymethyl)-1- methyl-1H-pyrazole-5-carboxylate (CAS 1208081-25-7, 15.0 g, 88.1 mmol) and diisopropylethyl amine (14.8 g, 115 mmol) in dichloromethane (250 mL). The mixture was stirred at 0 °C for 45 minutes after the addition was complete. The reaction mixture was washed with sat. aq NH4Cl, and the organic layer dried over sodium sulfate, filtered, and concentrated to give methyl 1-methyl-3-[(methylsulfonyl)oxy]methyl}-1H-pyrazole-5- carboxylate (5a, 22.6 g, >99%) as a yellow oil, which was used without further purification.1H NMR (400 MHz, CHLOROFORM-d) δ = 6.98 (s, 1H), 5.26 (s, 2H), 4.20 (s, 3H), 3.91 (s, 3H), 3.03 (s, 3H).
99% With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; 1 Preparation of Intermediate 5: Lithium 3-(methoxymethyl)-1-methyl-1H-pyrazole- 5-carboxylate. A solution of methanesulfonyl chloride (11.32 g, 98.8 mmol) in dichloromethane (50 mL) was added dropwise to a cooled (0 °C) mixture of methyl 3-(hydroxymethyl)-1- methyl-1H-pyrazole-5-carboxylate (CAS 1208081-25-7, 15.0 g, 88.1 mmol) and diisopropylethyl amine (14.8 g, 115 mmol) in dichloromethane (250 mL). The mixture was stirred at 0 °C for 45 minutes after the addition was complete. The reaction mixture was washed with sat. aq NH4Cl, and the organic layer dried over sodium sulfate, filtered, and concentrated to give methyl 1-methyl-3-[(methylsulfonyl)oxy]methyl}-1H-pyrazole-5- carboxylate (5a, 22.6 g, >99%) as a yellow oil, which was used without further purification.1H NMR (400 MHz, CHLOROFORM-d) δ = 6.98 (s, 1H), 5.26 (s, 2H), 4.20 (s, 3H), 3.91 (s, 3H), 3.03 (s, 3H).
99% With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; 4.2 2. Preparation of Intermediate 5: Lithium 3-(methoxymethyl)-1-methyl-1H- pyrazole-5-carboxylate. A solution of methanesulfonyl chloride (11.32 g, 98.8 mmol) in dichloromethane (50 mL) was added dropwise to a cooled (0 °C) mixture of methyl 3-(hydroxymethyl)-1- methyl-1H-pyrazole-5-carboxylate (CAS 1208081-25-7, 15.0 g, 88.1 mmol) and diisopropylethyl amine (14.8 g, 115 mmol) in dichloromethane (250 mL). The mixture was stirred at 0 °C for 45 minutes after the addition was complete. The reaction mixture was washed with sat. aq NH4Cl, and the organic layer dried over sodium sulfate, filtered, and concentrated to give methyl 1-methyl-3-[(methylsulfonyl)oxy]methyl}-1H-pyrazole-5- carboxylate (5a, 22.6 g, >99%) as a yellow oil, which was used without further purification.1H NMR (400 MHz, CHLOROFORM-d) δ = 6.98 (s, 1H), 5.26 (s, 2H), 4.20 (s, 3H), 3.91 (s, 3H), 3.03 (s, 3H).
With N-ethyl-N,N-diisopropylamine In dichloromethane Inert atmosphere; Cooling with ice; the fifth step: Add 1e (15g, 88.2mmol) into a 250mL reaction bottle,Dichloromethane (150 mL) and N,N-diisopropylethylamine (21 g, 158.7 mmol).Then, methylsulfonyl chloride (13g, 114.6mmol) was added to the reaction solution under nitrogen protection in an ice bath. The reaction solution was stirred in an ice bath for 1 hour and then spotted on TLC (petroleum ether:Ethyl acetate = 2:1, 254nm) reaction was complete. Add water (14 mL) dropwise to quench the reaction, add ammonium chloride aqueous solution (100 mL) to dilute, extract with methylene chloride (100 mL × 3), separate the organic phase, dry the organic phase with anhydrous sodium sulfate (150 g), reduce to Concentrate under pressure until no liquid drips out to obtain the target compound crude product 1f (23g). Use it directly for the next reaction.
With N-ethyl-N,N-diisopropylamine In dichloromethane Inert atmosphere; Cooling with ice; the fifth step: Add 1e (15g, 88.2mmol) into a 250mL reaction bottle,Dichloromethane (150 mL) and N,N-diisopropylethylamine (21 g, 158.7 mmol).Then, methylsulfonyl chloride (13g, 114.6mmol) was added to the reaction solution under nitrogen protection in an ice bath. The reaction solution was stirred in an ice bath for 1 hour and then spotted on TLC (petroleum ether:Ethyl acetate = 2:1, 254nm) reaction was complete. Add water (14 mL) dropwise to quench the reaction, add ammonium chloride aqueous solution (100 mL) to dilute, extract with methylene chloride (100 mL × 3), separate the organic phase, dry the organic phase with anhydrous sodium sulfate (150 g), reduce to Concentrate under pressure until no liquid drips out to obtain the target compound crude product 1f (23g). Use it directly for the next reaction.
With triethylamine; potassium iodide In dichloromethane at 20℃; 4.1 Step 1: Synthesis of 4-1: 180mL of methylene chloride, compound SM 4 (18.0g, 1.00eq), potassium iodide (668mg, 0.50eq), and triethylamine (16.0g, 1.50eq) were added to the 500mL three-mouth bottle, and then methane sulfonyl chloride (13.7g, 1.14eq) was added for 16 hours at room temperature. The reaction liquid was added to 100mL of water, stirred for 10 minutes, the organic layer was separated, and the organic phase was washed with 100mL of water, dried withNa2SO4, filtered, and the filtrate was concentrated in vacuum to obtain a crude product. Crude product was subjected to column chromatography to obtain compound 4-1 (yellow liquid, 10.5g, crude product).

  • 10
  • [ 1208081-25-7 ]
  • [ 2460256-08-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: dichloromethane / 0.75 h / 0 °C 2.1: 0.5 h / 70 °C 2.2: 5 h / 70 °C 3.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 16 h / 20 °C 4.1: N-ethyl-N,N-diisopropylamine; 1-propanephosphonic anhydride / dichloromethane; ethyl acetate / 126 h / 0 - 40 °C
  • 11
  • [ 117860-56-7 ]
  • [ 1208081-25-7 ]
YieldReaction ConditionsOperation in experiment
61% In tetrahydrofuran at 0 - 65℃; for 4h; Inert atmosphere; Synthesis of methyl 3-(hydroxymethyl)-l-methyl-1H-pyrazole-5-carboxylate To a solution of 5 -(methoxycarbonyl)- 1 -methyl - 1H-pyrazole-3 -carboxylic acid (5.70 g, 30.9 mmol) in THE (80 mL) at 0 °C under N2, was slowly added BH3 THF (61.9 mL, 61.9 mmol, 1 N). The reaction was allowed to warm to r.t. over 30 min and then heated to 65 °C for 4 h. After cooling to r.t., MeOH (12 mL) was slowly added, and then the solvent was removed under reduced pressure. The residue was re-dissolved in MeOH (12 mL), stirred for 20 min at r.t., and then then evaporated to dryness. The residue was diluted with water and extracted with DCM (50.0 mL × 3). The combined organic phases were washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The crude mixture was then purified via silica gel chromatography (33→100% EA in PE) to give methyl 3 -(hydroxymethyl)- 1 -methyl - 1H-pyrazole -5 -carboxylate (3.2 g, yield: 61%) as a white solid. LC-MS ESI (m/z): 171 [M+H]+.
61% In tetrahydrofuran at 0 - 65℃; for 4h; Inert atmosphere; Synthesis of methyl 3-(hydroxymethyl)-l-methyl-1H-pyrazole-5-carboxylate To a solution of 5 -(methoxycarbonyl)- 1 -methyl - 1H-pyrazole-3 -carboxylic acid (5.70 g, 30.9 mmol) in THE (80 mL) at 0 °C under N2, was slowly added BH3 THF (61.9 mL, 61.9 mmol, 1 N). The reaction was allowed to warm to r.t. over 30 min and then heated to 65 °C for 4 h. After cooling to r.t., MeOH (12 mL) was slowly added, and then the solvent was removed under reduced pressure. The residue was re-dissolved in MeOH (12 mL), stirred for 20 min at r.t., and then then evaporated to dryness. The residue was diluted with water and extracted with DCM (50.0 mL × 3). The combined organic phases were washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The crude mixture was then purified via silica gel chromatography (33→100% EA in PE) to give methyl 3 -(hydroxymethyl)- 1 -methyl - 1H-pyrazole -5 -carboxylate (3.2 g, yield: 61%) as a white solid. LC-MS ESI (m/z): 171 [M+H]+.
20 g With borane-THF In tetrahydrofuran at 0 - 40℃; Inert atmosphere; 3 Step 3: Synthesis of compound C-4 Under nitrogen protection, suspend C-3 (25.0 g, 135.7 mmol) in tetrahydrofuran (200 mL), cool to 0°C, and drop borane tetrahydrofuran solution (1M, 407 mL). After the drop is complete, slowly heat to 40°C and react at 40°C for 5 hours. Reduce to 0°C, carefully drop methanol (200 mL), then slowly heat to room temperature and stir overnight. Concentrate the system, and purify the crude product by column chromatography (petroleum ether: ethyl acetate 5:1 to 2:1) to obtain C-4 (20.0 g).
  • 12
  • [ 1208081-25-7 ]
  • [ 1783796-51-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine / dichloromethane / 1 h / Inert atmosphere; Cooling with ice 2: 80 min / 20 - 70 °C 3: lithium hydroxide monohydrate; water / tetrahydrofuran / 1 h / 20 °C
  • 13
  • [ 1031351-95-7 ]
  • [ 1208081-25-7 ]
YieldReaction ConditionsOperation in experiment
55 % With sodium tetrahydroborate In tetrahydrofuran Cooling with ice; the fourth step: Add 1d (27g, 0.16mol) and tetrahydrofuran (270mL) into a 500mL reaction bottle,Sodium borohydride (7g, 0.19mol) was slowly added to the reaction solution in three batches under ice bath.The reaction solution was stirred in an ice bath for 1.5 hours and then the TLC spot plate (petroleum ether: ethyl acetate = 2:1, 254 nm) reacted completely. Add water (14 mL) dropwise to quench the reaction, add ammonium chloride aqueous solution (200 mL) to dilute, extract with ethyl acetate (100 mL Concentrate under pressure until no liquid drips out to obtain crude product (30g).The crude product was further purified by normal phase column (eluent: petroleum ether: ethyl acetate = 2:1, 254 nm) to obtain the target compound 1e (15 g, yield: 55%).
55 % With sodium tetrahydroborate In tetrahydrofuran Cooling with ice; the fourth step: Add 1d (27g, 0.16mol) and tetrahydrofuran (270mL) into a 500mL reaction bottle,Sodium borohydride (7g, 0.19mol) was slowly added to the reaction solution in three batches under ice bath.The reaction solution was stirred in an ice bath for 1.5 hours and then the TLC spot plate (petroleum ether: ethyl acetate = 2:1, 254 nm) reacted completely. Add water (14 mL) dropwise to quench the reaction, add ammonium chloride aqueous solution (200 mL) to dilute, extract with ethyl acetate (100 mL Concentrate under pressure until no liquid drips out to obtain crude product (30g).The crude product was further purified by normal phase column (eluent: petroleum ether: ethyl acetate = 2:1, 254 nm) to obtain the target compound 1e (15 g, yield: 55%).
  • 14
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  • [ 1208081-25-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: acetic acid / water / 1 h / 60 °C 2: sodium tetrahydroborate / tetrahydrofuran / 1.5 h / Cooling with ice
 

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