Acetic Acid → cis-N-{3-[1-(5-fluoro-pyridin-2-ylmethyl)-4-hydroxy-2-oxo-2,4a,5,6,7,7a-hexahydro-1H-[1]pyrindin-3-yl]-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide

HRID 731248Notes

Reaction equation

HRID 731248 reaction equation
C([O:3][C:4]([C@@H:6]1[CH2:10][CH2:9][CH2:8][C@@H:7]1[N:11]([CH2:32][C:33]1[CH:38]=[CH:37][C:36]([F:39])=[CH:35][N:34]=1)[C:12](=[O:31])[CH2:13][C:14]1[NH:19][C:18]2[CH:20]=[CH:21][C:22]([NH:24][S:25]([CH3:28])(=[O:27])=[O:26])=[CH:23][C:17]=2[S:16](=[O:30])(=[O:29])[N:15]=1)=O)C.[O-]CC.[Na+].C(O)(=O)C>C(O)C>[F:39][C:36]1[CH:37]=[CH:38][C:33]([CH2:32][N:11]2[C@@H:7]3[C@@H:6]([CH2:10][CH2:9][CH2:8]3)[C:4]([OH:3])=[C:13]([C:14]3[NH:19][C:18]4[CH:20]=[CH:21][C:22]([NH:24][S:25]([CH3:28])(=[O:26])=[O:27])=[CH:23][C:17]=4[S:16](=[O:30])(=[O:29])[N:15]=3)[C:12]2=[O:31])=[N:34][CH:35]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 2723922Sodium ethoxideHCID 69063590cis-2-{(5-Fluoro-pyridin-2-ylmethyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclopentane-carboxylic acid ethyl ester

Product 1

HCID 137194573cis-N-{3-[1-(5-fluoro-pyridin-2-ylmethyl)-4-hydroxy-2-oxo-2,4a,5,6,7,7a-hexahydro-1H-[1]pyrindin-3-yl]-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamideYield 66.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
60 °C

Procedure

A solution of cis-2-{(5-fluoro-pyridin-2-ylmethyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclopentane-carboxylic acid ethyl ester (0.085 g, 0.146 mmol) in ethanol (2 mL) was treated with a 21% w/w solution of sodium ethoxide in ethanol (0.218 mL) and stirred for 2 h at 60° C. Glacial acetic acid (0.200 mL) was added, the solvents were removed in vacuo, and the residue was purified by prep-HPLC [Column Luna 5μ C18 (2) 100 Å AXIA 50×21.2 mm, 5 micron, 30%-90% in 7 min @ 30 mL/min flow rate, 0.05% trifluoroacetic acid in acetonitrile/0.05% trifluoroacetic acid in water] to afford the desired product, cis-N-{3-[1-(5-fluoro-pyridin-2-ylmethyl)-4-hydroxy-2-oxo-2,4a,5,6,7,7a-hexahydro-1H-[1]pyrindin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide (0.052 g, 0.097 mmol, 66.5%), as a white solid. 1H NMR (400 MHz, DMSO-d6) δ: 1.47-1.69 (3H, m), 1.96-2.14 (3H, m), 3.06 (3H, s), 3.95-4.01 (1H, m), 4.61 (1H, bs), 4.96 (1H, d, J=16.5 Hz), 7.46-7.52 (2H, m), 7.56-7.58 (2H, m), 7.67-7.72 (1H, m), 8.51 (1H, d, J=3.5 Hz), 10.18 (1H, s). LC-MS (ESI) calcd for C22H22FN5O6S2 535.10, found 536.4 [M+H+].

Workup

  1. customthe solvents were removed in vacuo
  2. customthe residue was purified by prep-HPLC [Column Luna 5μ C18 (2) 100 Å AXIA 50×21.2 mm, 5 micron, 30%-90% in 7 min

Sources & evidence

ORD record
ord-9828cccf4a7f4d699d3492a83bb7816e
Source dataset
uspto-grants-2009_09
Patent number
US07582626B2

Reaction notes

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