Sarcosine → cis-2-amino-ethanesulfonic acid {3-[1-(4-fluoro-benzyl)-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}-amide

HRID 731305Notes

Reaction equation

HRID 731305 reaction equation
N(CC(O)=O)C.[NH2:7][CH2:8][CH2:9][S:10]([NH2:13])(=[O:12])=[O:11].[F:14][C:15]1[CH:45]=[CH:44][C:18]([CH2:19][N:20]2[C@@H:28]3[C@@H:24]([CH2:25][CH2:26][CH2:27]3)[C:23]([OH:29])=[C:22]([C:30]3[NH:35][C:34]4[CH:36]=[CH:37][C:38](I)=[CH:39][C:33]=4[S:32](=[O:42])(=[O:41])[N:31]=3)[C:21]2=[O:43])=[CH:17][CH:16]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[Cu]I>[F:14][C:15]1[CH:45]=[CH:44][C:18]([CH2:19][N:20]2[C@@H:28]3[C@@H:24]([CH2:25][CH2:26][CH2:27]3)[C:23]([OH:29])=[C:22]([C:30]3[NH:35][C:34]4[CH:36]=[CH:37][C:38]([NH:13][S:10]([CH2:9][CH2:8][NH2:7])(=[O:12])=[O:11])=[CH:39][C:33]=4[S:32](=[O:42])(=[O:41])[N:31]=3)[C:21]2=[O:43])=[CH:17][CH:16]=1

Participants

6

Reactant 4

HCID 1088SarcosineHCID 62657Potassium Phosphate, TribasicHCID 101263TaurinamideHCID 135955738(4aR,7aS)-1-[(4-fluorophenyl)methyl]-4-hydroxy-3-(7-iodo-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazin-3-yl)-5,6,7,7a-tetrahydro-4aH-cyclopenta[b]pyridin-2-one

Product 1

HCID 137194579cis-2-amino-ethanesulfonic acid {3-[1-(4-fluoro-benzyl)-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}-amideYield 10.1%

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Conditions

Temperature
100 °C

Procedure

A reaction flask was charged with copper(I) iodide (268 mg, 1.41 mmol), sarcosine (N-methyl glycine) (188 mg, 2.11 mmol), 2-amino-ethanesulfonic acid amide (1.80 g, 11.2 mmol), cis-1-(4-fluoro-benzyl)-4-hydroxy-3-(7-iodo-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-1,4a,5,6,7,7a-hexahydro-[1]pyrindin-2-one (1.0 g, 1.76 mmol) and potassium phosphate (2.61 g, 12.32 mmol). The flask was degassed and backfilled with nitrogen, and then anhydrous N,N-dimethylformamide (16 mL) was added. The resulting suspension was vigorously stirred at 100° C. for 2 h and then at 120° C. for 1.5 h, cooled to 25° C., passed through a plug of Celite and rinsed with 10% methanol-dichloromethane. The filtrate was concentrated in vacuo, and the residue was purified by prep-HPLC [Column ODS-A 5μ 100 Å, 150×21.2 mm, 5 micron, 30%-100% in 13.5 min @ 22 mL/min flow rate, 0.05% trifluoroacetic acid in acetonitrile/0.05% trifluoroacetic acid in water] to afford the desired product, cis-2-amino-ethanesulfonic acid {3-[1-(4-fluoro-benzyl)-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}-amide (100 mg, 0.178 mmol, 10%), as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ: 1.52 (3H, m), 1.99 (2H, m), 2.06 (1H, m), 3.17 (2H, m), 3.30 (1H, m), 3.46 (2H, t, J=6.8 Hz), 3.86 (1H, bs), 4.48 (1H, bs), 4.90 (1H, d, J=14.8 Hz), 7.16 (2H, m), 7.39 (2H, m), 7.51 (1H, m), 7.61 (2H, m), 7.82 (3H, s), 10.55 (1H, s). LC-MS (ESI) calcd for C24H26FN5O6S2 563.13, found 564.2 [M+H+].

Workup

  1. customThe flask was degassed
  2. additionanhydrous N,N-dimethylformamide (16 mL) was added
  3. waitat 120° C. for 1.5 h
  4. temperaturecooled to 25° C.
  5. washrinsed with 10% methanol-dichloromethane
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe residue was purified by prep-HPLC [Column ODS-A 5μ 100 Å, 150×21.2 mm, 5 micron, 30%-100% in 13.5 min @ 22 mL/min flow rate, 0.05% trifluoroacetic acid in acetonitrile/0.05% trifluoroacetic acid in water]

Sources & evidence

ORD record
ord-30430e383d76460090df5a9ff5051e7e
Source dataset
uspto-grants-2009_09
Patent number
US07582626B2

Reaction notes

Loading…