Sarcosine → cyclopropanesulfonic acid {3-(1R,2S,7R,8S)-[6-hydroxy-3-(3-methyl-butyl)-4-oxo-3-aza-tricyclo[6.2.1.02,7]undec-5-en-5-yl]-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-7-yl}-amide

HRID 884258Notes

Reaction equation

HRID 884258 reaction equation
N(CC(O)=[O:5])C.[CH:7]1([S:10]([NH2:13])(=[O:12])=[O:11])[CH2:9][CH2:8]1.[OH:14][C:15]1[C@H:24]2[C@H:19]([C@H:20]3[CH2:25][C@@H:23]2[CH2:22][CH2:21]3)[N:18]([CH2:26][CH2:27][CH:28]([CH3:30])[CH3:29])[C:17](=[O:31])[C:16]=1[C:32]1[NH:37][C:36]2[CH:38]=[CH:39][C:40](I)=[CH:41][C:35]=2[S:34](=[O:44])(=[O:43])[N:33]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[Cu]I>[CH:7]1([S:10]([OH:12])(=[O:5])=[O:11])[CH2:9][CH2:8]1.[OH:14][C:15]1[C@H:24]2[C@H:19]([C@H:20]3[CH2:25][C@@H:23]2[CH2:22][CH2:21]3)[N:18]([CH2:26][CH2:27][CH:28]([CH3:30])[CH3:29])[C:17](=[O:31])[C:16]=1[C:32]1[NH:37][C:36]2[CH:38]=[CH:39][C:40]([NH:13][S:10]([CH:7]3[CH2:9][CH2:8]3)(=[O:12])=[O:11])=[CH:41][C:35]=2[S:34](=[O:44])(=[O:43])[N:33]=1

Participants

7

Reactant 4

HCID 1088SarcosineHCID 62657Potassium Phosphate, TribasicHCID 15765418CyclopropanesulfonamideHCID 136402483(1R,2S,7R,8S)-6-hydroxy-5-(7-iodo-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)-3-(3-methyl-butyl)-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-one

Product 2

HCID 10419166Cyclopropanesulfonic AcidHCID 136404887cyclopropanesulfonic acid {3-(1R,2S,7R,8S)-[6-hydroxy-3-(3-methyl-butyl)-4-oxo-3-aza-tricyclo[6.2.1.02,7]undec-5-en-5-yl]-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-7-yl}-amideYield 27.1%

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 (20 mg, 0.11 mmol), sarcosine (N-methyl glycine) (14.7 mg, 0.17 mmol), cyclopropanesulfonamide (125 mg, 1.04 mmol), (1R,2S,7R,8S)-6-hydroxy-5-(7-iodo-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-3-(3-methyl-butyl)-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-one (prepared as described in Example 34, 115 mg, 0.21 mmol) and potassium phosphate (176 mg, 0.83 mmol). The flask was degassed and backfilled with nitrogen, and then anhydrous N,N-dimethylformamide (5 mL) was added. The resulting suspension was vigorously stirred at 100° C. for 3 h, and then allowed to cool to 25° C. The mixture was 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 Luna 5μ C18 (2) 100 Å AXIA 150×21.2 mm, 5 micron, 30%-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, cyclopropanesulfonic acid {3-(1R,2S,7R,8S)-[6-hydroxy-3-(3-methyl-butyl)-4-oxo-3-aza-tricyclo[6.2.1.02,7]undec-5-en-5-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-amide (25 mg, 0.046 mmol, 22%), as a white solid. 1H NMR (400 MHz, DMSO-d6) δ: 0.92-0.98 (10H, m), 1.20-1.64 (9H, m), 2.52 (1H, m), 2.62 (1H, s), 2.68 (1H, m), 3.00 (1H, d, J=9.6 Hz), 3.07 (1H, m), 3.61 (1H, d, J=10.4 Hz), 3.66 (1H, m), 7.50-7.59 (3H, m), 10.17 (1H, s). LC-MS (ESI) calcd for C25H32N4O6S2 548.18, found 549.4 [M+H+].

Workup

  1. customThe flask was degassed
  2. additionanhydrous N,N-dimethylformamide (5 mL) was added
  3. temperatureto cool to 25° C
  4. washrinsed with 10% methanol/dichloromethane
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was purified by prep-HPLC [Column Luna 5μ C18 (2) 100 Å AXIA 150×21.2 mm, 5 micron, 30%-95% in 7 min

Sources & evidence

ORD record
ord-e290de41a01f49be89afe2544ea3276b
Source dataset
uspto-grants-2012_08
Patent number
US08236948B2

Reaction notes

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