Pyridine → N-(4-tert-butyl-3-hydroxy-phenyl)-3,4-dihydro-2H-1,4-benzothiazine-2-carboxamide

HRID 1465178Notes

Reaction equation

HRID 1465178 reaction equation
[S:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[NH:4][CH2:3][CH:2]1[C:11]([OH:13])=O.[NH2:14][C:15]1[CH:16]=[CH:17][C:18]([C:22]([CH3:25])([CH3:24])[CH3:23])=[C:19]([OH:21])[CH:20]=1.N1C=CC=CC=1>ClCCl>[C:22]([C:18]1[CH:17]=[CH:16][C:15]([NH:14][C:11]([CH:2]2[CH2:3][NH:4][C:5]3[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=3[S:1]2)=[O:13])=[CH:20][C:19]=1[OH:21])([CH3:25])([CH3:23])[CH3:24]

Participants

5

Reactant 3

HCID 1049PyridineHCID 447914203,4-dihydro-2H-1,4-benzothiazine-2-carboxylic acidHCID 574702095-Amino-2-(tert-butyl)phenol

Product 1

HCID 59395005N-(4-tert-butyl-3-hydroxy-phenyl)-3,4-dihydro-2H-1,4-benzothiazine-2-carboxamideYield 36.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 3,4-dihydro-2H-1,4-benzothiazine-2-carboxylic acid (80 mg, 0.41 mmol) and 5-amino-2-tert-butyl-phenol (67 mg, 0.41 mmol) in dichloromethane (3 mL) was treated with propane phosphonic acid anhydride (610 μL of 50% w/w in ethyl acetate, 1.02 mmol) and pyridine (99 μL, 1.2 mmol) and stirred for 30 min at room temperature. The reaction was washed with water, dried over Na2SO4, and concentrated in vacuo. HPLC purification (20-99% CH3CN/0.05% TFA) provided N-(4-tert-butyl-3-hydroxy-phenyl)-3,4-dihydro-2H-1,4-benzothiazine-2-carboxamide (51 mg, 36% yield). LC/MS m/z 343.2 [M+H]+. 1H NMR (400.0 MHz, DMSO-d6) δ 10.07 (s, 1H), 9.38 (s, 1H), 7.20 (d, J=2.0 Hz, 1H), 7.03 (d, J=8.4 Hz, 1H), 6.93 (dd, J=1.1, 7.7 Hz, 1H), 6.88-6.83 (m, 2H), 6.58 (d, J=7.5 Hz, 1H), 6.51-6.47 (t, J=7.5, 1H), 3.92 (dd, J=3.0, 8.0 Hz, 1H), 3.72 (dd, J=3.0, 12.3 Hz, 1H), 3.53 (dd, J=8.1, 12.3 Hz, 1H), 1.31 (s, 9H).

Workup

  1. washThe reaction was washed with water
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customHPLC purification (20-99% CH3CN/0.05% TFA)

Sources & evidence

ORD record
ord-ecd9eebb18944f69a029abdd6e9a0217
Source dataset
uspto-grants-2015_04
Patent number
US08999976B2

Reaction notes

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