Benzyl Alcohol → benzyl [N-{3-[(1R,2S,7R,8S)-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]thiadiazin-7-yl}-sulfamoyl]carbamate

HRID 548360Notes

Reaction equation

HRID 548360 reaction equation
[CH2:1]([OH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[S:10]([N:13]=[C:14]=[O:15])(=[O:12])=[O:11].C(N(CC)CC)C.[NH2:23][C:24]1[CH:56]=[CH:55][C:27]2[NH:28][C:29]([C:34]3[C:35](=[O:54])[N:36]([CH2:46][C:47]4[CH:52]=[CH:51][C:50]([F:53])=[CH:49][CH:48]=4)[C@@H:37]4[C@H:42]([C:43]=3[OH:44])[C@@H:41]3[CH2:45][C@H:38]4[CH2:39][CH2:40]3)=[N:30][S:31](=[O:33])(=[O:32])[C:26]=2[CH:25]=1>ClCCl>[F:53][C:50]1[CH:49]=[CH:48][C:47]([CH2:46][N:36]2[C:35](=[O:54])[C:34]([C:29]3[NH:28][C:27]4[CH:55]=[CH:56][C:24]([NH:23][S:10]([NH:13][C:14](=[O:15])[O:8][CH2:1][C:2]5[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=5)(=[O:12])=[O:11])=[CH:25][C:26]=4[S:31](=[O:32])(=[O:33])[N:30]=3)=[C:43]([OH:44])[C@H:42]3[C@@H:37]2[C@H:38]2[CH2:45][C@@H:41]3[CH2:40][CH2:39]2)=[CH:52][CH:51]=1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 8471TriethylamineHCID 70918Chlorosulfonyl isocyanateHCID 136402488(1R,2S,7R,8S)-5-(7-amino-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

Product 1

HCID 136404888benzyl [N-{3-[(1R,2S,7R,8S)-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]thiadiazin-7-yl}-sulfamoyl]carbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Benzyl alcohol (35 μL, 0.338 mmol) was dissolved in dichloromethane (3 mL) and cooled to 0° C. Chlorosulfonyl isocyanate (29.4 μL, 0.338 mmol) was added and the mixture was stirred at 0° C. for 2.5 h. Triethylamine (47 μL, 0.34 mmol) followed by a solution of (1R,2S,7R,8S)-5-(7-amino-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 (prepared as described in Example 30, 81.4 mg, 0.169 mmol) in dichloromethane (2 mL) were added at 0° C. and the mixture was stirred at 25° C. for 17 h. The mixture was extracted with water (2×2 mL) and saturated aqueous brine solution (2 mL). The organic layer was concentrated in vacuo and further dried for 16 h under high vacuum to afford the crude product, benzyl [N-{3-[(1R,2S,7R,8S)-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]thiadiazin-7-yl}-sulfamoyl]carbamate, which was used in the next step without any further purification. LC-MS (ESI) calcd for C32H30FN5O8S2 695.15, found 696.6 [M+H+].

Workup

  1. additionwere added at 0° C.
  2. stirringthe mixture was stirred at 25° C. for 17 h
  3. extractionThe mixture was extracted with water (2×2 mL) and saturated aqueous brine solution (2 mL)
  4. concentrationThe organic layer was concentrated in vacuo
  5. customfurther dried for 16 h under high vacuum

Sources & evidence

ORD record
ord-2a9066dadc9e42a2afe522cfe7bd72a8
Source dataset
uspto-grants-2011_05
Patent number
US07939524B2

Reaction notes

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