Water → n-{3-Tert-butyl-1-[(2r)-tetrahydrofuran-2-ylmethyl]-1h-pyrazol-5-yl}-5-chloro-2-methoxybenzamide

HRID 717244Notes

Reaction equation

HRID 717244 reaction equation
Cl.[C:2]([C:6]1[CH:10]=[C:9]([NH2:11])[N:8]([CH2:12][C@H:13]2[CH2:17][CH2:16][CH2:15][O:14]2)[N:7]=1)([CH3:5])([CH3:4])[CH3:3].C(N(CC)CC)C.[Cl:25][C:26]1[CH:27]=[CH:28][C:29]([O:35][CH3:36])=[C:30]([CH:34]=1)[C:31](Cl)=[O:32].O>C(Cl)Cl>[C:2]([C:6]1[CH:10]=[C:9]([NH:11][C:31](=[O:32])[C:30]2[CH:34]=[C:26]([Cl:25])[CH:27]=[CH:28][C:29]=2[O:35][CH3:36])[N:8]([CH2:12][C@H:13]2[CH2:17][CH2:16][CH2:15][O:14]2)[N:7]=1)([CH3:5])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 123841765-Chloro-2-methoxybenzoyl chloride2×HCID 67493417(R)-3-tert-butyl-1-((tetrahydrofuran-2-yl)methyl)-1H-pyrazol-5-amine hydrochloride

Product 1

HCID 67544623n-{3-Tert-butyl-1-[(2r)-tetrahydrofuran-2-ylmethyl]-1h-pyrazol-5-yl}-5-chloro-2-methoxybenzamideYield 80%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To the mixture of Example 45B (1.25 g, 5.6 mmol) in CH2Cl2 (50 mL) cooled with an ice-bath was added triethylamine (2.3 mL, 16.8 mmol), and 5-chloro-2-methoxybenzoyl chloride (the product from Step A of Example 11C) (1.15 g, 5.6 mmol) dropwise. The mixture was stirred at ambient temperature for 2 h, then treated with water (50 mL) and CH2Cl2 (50 mL). The organic layer was washed with brine and concentrated. Purification by flash chromatography (silica gel, Et3N/MeOH/EtOAc, (1:10:90) in hexane in 10-40% gradient) afforded 1.75 g (80%) of the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.24 (s, 9H), 1.46-1.59 (m, 1H), 1.61-1.82 (m, 2H), 1.84-1.97 (m, 1H), 3.54-3.76 (m, 2H), 3.97 (s, 3H), 4.01-4.23 (m, 3H), 6.31 (s, 1H), 7.28 (d, J=8.72 Hz, 1H), 7.62 (dd, J=8.73, 2.78 Hz, 1H), 7.81 (d, J=2.78 Hz, 1H), 10.25 (s, 1H)); MS (ESI) m/z 392 [M+H]+, 390 [M−H].

Workup

  1. washThe organic layer was washed with brine
  2. concentrationconcentrated
  3. customPurification by flash chromatography (silica gel, Et3N/MeOH/EtOAc, (1:10:90) in hexane in 10-40% gradient)

Sources & evidence

ORD record
ord-0d87c50e43a74364b6c968d9bd35630f
Source dataset
uspto-grants-2015_11
Patent number
US09193713B2

Reaction notes

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