HCID 135955765, compound → HCID 135955766, compound

HRID 731354Notes

Reaction equation

HRID 731354 reaction equation
[O:1]=[S:2]1(=[O:38])[CH2:6][CH2:5][CH:4]=[C:3]1[C:7]1[CH:37]=[CH:36][C:10]2[NH:11][C:12]([C:17]3[C:18](=[O:35])[N:19]([CH2:27][C:28]4[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=4)[C@@H:20]4[C@H:24]([C:25]=3[OH:26])[CH2:23][CH2:22][CH2:21]4)=[N:13][S:14](=[O:16])(=[O:15])[C:9]=2[CH:8]=1>CN(C)C=O.CO.[Pd]>[O:38]=[S:2]1(=[O:1])[CH2:6][CH2:5][CH2:4][CH:3]1[C:7]1[CH:37]=[CH:36][C:10]2[NH:11][C:12]([C:17]3[C:18](=[O:35])[N:19]([CH2:27][C:28]4[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=4)[C@@H:20]4[C@H:24]([C:25]=3[OH:26])[CH2:23][CH2:22][CH2:21]4)=[N:13][S:14](=[O:15])(=[O:16])[C:9]=2[CH:8]=1

Participants

5

Reactant 1

HCID 135955765HCID 135955765, compound

Product 1

HCID 135955766HCID 135955766, compound

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

(4aR,7aS)-3-[7-(1,1-Dioxo-4,5-dihydro-1H-1λ6-thiophen-2-yl)-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl]-1-(4-fluoro-benzyl)-4-hydroxy-1,4a,5,6,7,7a-hexahydro-[1]pyrindin-2-one (prepared as described in Example 44, 45 mg, 0.081 mmol) was dissolved in a 1:5 mixture of N,N-dimethylformamide and methanol (12 mL). 5% Palladium on charcoal (100 mg) was added. The flask was degassed and backfilled with hydrogen gas via balloon. The mixture was stirred at 25° C. for 16 h. The mixture was passed through a plug of Celite, washed with 10% methanol/dichloromethane, and the filtrate was concentrated in vacuo. The residue was purified by prep-HPLC [Column Luna 5μ C18 (2) 100 Å AXIA 50×21.2 mm, 5 micron, 40-95% 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 as an inseparable mixture of two diastereomers, (4aR,7aS)-3-[7-(1,1-dioxo-tetrahydro-1λ6-thiophen-2-yl)-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl]-1-(4-fluoro-benzyl)-4-hydroxy-1,4a,5,6,7,7a-hexahydro-[1]pyrindin-2-one (20 mg, 0.036 mmol, 44%), as a white powder. 1H NMR (400 MHz, DMSO-d6) δ: 1.44-1.60 (3H, m), 1.95-2.40 (10H, m), 3.22-3.36 (3H, m), 3.86 (1H, bs), 4.47 (1H, d, J=14.4 Hz), 4.56 (1H, dd, J=12.4, 8.0 Hz), 4.91 (1H, d, J=15.2 Hz), 7.15 (2H, t, J=8.4 Hz), 7.39 (2H, m), 7.61 (1H, d, J=8.8 Hz), 7.71 (1H, dd, J=8.4, 2.4 Hz), 7.82 (1H, s). LC-MS (ESI) calcd for C26H26FN3O6S2 559.12, found 560.3 [M+H+].

Workup

  1. customThe flask was degassed
  2. washwashed with 10% methanol/dichloromethane
  3. concentrationthe filtrate was concentrated in vacuo
  4. customThe residue was purified by prep-HPLC [Column Luna 5μ C18 (2) 100 Å AXIA 50×21.2 mm, 5 micron, 40-95% in 7 min

Sources & evidence

ORD record
ord-0235a56b592a41228687bd10f1365cf7
Source dataset
uspto-grants-2009_09
Patent number
US07582626B2

Reaction notes

Loading…