Sodium Iodide → {(S)-1-[(S)-9-(6-bromo-2-methoxy-naphthalen-1-ylmethyl)-3-methyl-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-ylcarbamoyl]-ethyl}-methyl-carbamic acid tert-butyl ester

HRID 1055444Notes

Reaction equation

HRID 1055444 reaction equation
[C:1]([O:5][C:6](=[O:27])[N:7]([CH3:26])[C@H:8]([C:10](=[O:25])[NH:11][C@@H:12]1[C:18](=[O:19])[NH:17][C:16]2[CH:20]=[CH:21][C:22]([CH3:24])=[CH:23][C:15]=2[O:14][CH2:13]1)[CH3:9])([CH3:4])([CH3:3])[CH3:2].[Na+].[I-].C([O-])([O-])=O.[Cs+].[Cs+].[Br:36][C:37]1[CH:38]=[C:39]2[C:44](=[CH:45][CH:46]=1)[C:43]([CH2:47]Cl)=[C:42]([O:49][CH3:50])[CH:41]=[CH:40]2>CN(C=O)C.CCOC(C)=O>[C:1]([O:5][C:6](=[O:27])[N:7]([C@H:8]([C:10](=[O:25])[NH:11][C@@H:12]1[C:18](=[O:19])[N:17]([CH2:47][C:43]2[C:44]3[C:39](=[CH:38][C:37]([Br:36])=[CH:46][CH:45]=3)[CH:40]=[CH:41][C:42]=2[O:49][CH3:50])[C:16]2[CH:20]=[CH:21][C:22]([CH3:24])=[CH:23][C:15]=2[O:14][CH2:13]1)[CH3:9])[CH3:26])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 7371226-Bromo-1-(chloromethyl)-2-methoxynaphthaleneHCID 90037667methyl-[(S)-1-((S)-3-methyl-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-ylcarbamoyl)-ethyl]-carbamic acid tert-butyl ester

Product 1

HCID 90037314{(S)-1-[(S)-9-(6-bromo-2-methoxy-naphthalen-1-ylmethyl)-3-methyl-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-ylcarbamoyl]-ethyl}-methyl-carbamic acid tert-butyl esterYield 16%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of methyl-[(S)-1-((S)-3-methyl-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-ylcarbamoyl)-ethyl]-carbamic acid tert-butyl ester (241 mg, 639 μmol, Eq: 1.00), NaI (95.7 mg, 639 μmol, Eq: 1.00), Cs2CO3 (312 mg, 958 μmol, Eq: 1.50), 6-bromo-1-(chloromethyl)-2-methoxynaphthalene (219 mg, 766 μmol, Eq: 1.20) in DMF (3 mL) was stirred at RT for 1 h and at 50° C. for 1 h. The mixture was diluted with EtOAc, washed with water, brine, dried over Na2SO4, filtered and concentrated. The resulting material was purified by silica gel chromatography to afford {(S)-1-[(S)-9-(6-bromo-2-methoxy-naphthalen-1-ylmethyl)-3-methyl-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-ylcarbamoyl]-ethyl}-methyl-carbamic acid tert-butyl ester (63 mg, 16%) as an oil.

Workup

  1. washwashed with water, brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe resulting material was purified by silica gel chromatography

Sources & evidence

ORD record
ord-d36bf9972b0443f6a0b469e729fad331
Source dataset
uspto-grants-2016_07
Patent number
US09394263B2

Reaction notes

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