Hydrochloric Acid → (1R,2S,7R,8S)-5-(7-Aminomethyl-1,1-dioxo-1,4-dihydro-1lambda6 benzo[1,2,4]thiadiazin-3-yl)-3-(4-fluoro-benzyl)-6-hydroxy-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-one hydrochloride

HRID 421460Notes

Reaction equation

HRID 421460 reaction equation
[F:1][C:2]1[CH:35]=[CH:34][C:5]([CH2:6][N:7]2[C:16](=[O:17])[C:15]([C:18]3[NH:23][C:22]4[CH:24]=[CH:25][C:26]([C:28]#[N:29])=[CH:27][C:21]=4[S:20](=[O:31])(=[O:30])[N:19]=3)=[C:14]([OH:32])[C@H:13]3[C@@H:8]2[C@H:9]2[CH2:33][C@@H:12]3[CH2:11][CH2:10]2)=[CH:4][CH:3]=1.[ClH:36]>CO.[Pd]>[ClH:36].[NH2:29][CH2:28][C:26]1[CH:25]=[CH:24][C:22]2[NH:23][C:18]([C:15]3[C:16](=[O:17])[N:7]([CH2:6][C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:35][CH:34]=4)[C@@H:8]4[C@H:13]([C:14]=3[OH:32])[C@@H:12]3[CH2:33][C@H:9]4[CH2:10][CH2:11]3)=[N:19][S:20](=[O:31])(=[O:30])[C:21]=2[CH:27]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 136395899(1R,2S,7R,8S)-3-[3-(4-fluoro-benzyl)-6-hydroxy-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]thiadiazine-7-carbonitrile

Product 1

HCID 136395900(1R,2S,7R,8S)-5-(7-Aminomethyl-1,1-dioxo-1,4-dihydro-1lambda6 benzo[1,2,4]thiadiazin-3-yl)-3-(4-fluoro-benzyl)-6-hydroxy-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-one hydrochloride

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

(1R,2S,7R,8S)-3-[3-(4-Fluoro-benzyl)-6-hydroxy-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]thiadiazine-7-carbonitrile (0.38 g, 0.77 mmol) was dissolved in methanol (required gentle heating via heat gun). Concentrated aqueous hydrochloric acid solution (5 mL) was added followed by 10% palladium on carbon (−150 mg). The mixture was degassed and backfilled with hydrogen gas via balloon. The mixture stirred at 25° C. for 3 h. The mixture was passed through a plug of Celite, eluting with additional methanol (200 mL). The filtrate was concentrated in vacuo to afford the desired product, (1R,2S,7R,8S)-5-(7-aminomethyl-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-3-(4-fluoro-benzyl)-6-hydroxy-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-one hydrochloride (˜0.77 mmol), as a pale yellow solid. The solid was used directly in the next step without further purification or characterization. LC-MS (ESI) calculated for C25H25FN4O4S 496.16. found 497.3 [M+H+].

Workup

  1. temperaturegentle heating
  2. temperaturevia heat gun)
  3. customThe mixture was degassed
  4. washeluting with additional methanol (200 mL)
  5. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-eba7b819d8854658ac69ad753f6d25d8
Source dataset
uspto-grants-2012_01
Patent number
US08097613B2

Reaction notes

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