Sodium Iodide → tert-butyl methyl((S)-1-((2S,3S)-2-methyl-5-((3-methylquinolin-4-yl)methyl)-1-(2-(methylsulfonyl)acetyl)-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl)carbamate

HRID 1486053Notes

Reaction equation

HRID 1486053 reaction equation
[CH3:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH2:12]O)=[CH:9][CH:8]=[CH:7][CH:6]=2.C(N(CC)CC)C.CS(Cl)(=O)=O.[CH3:26][N:27]([C@@H:35]([CH3:59])[C:36]([NH:38][C@H:39]1[C@H:45]([CH3:46])[N:44]([C:47](=[O:53])[CH2:48][S:49]([CH3:52])(=[O:51])=[O:50])[C:43]2[CH:54]=[CH:55][CH:56]=[CH:57][C:42]=2[NH:41][C:40]1=[O:58])=[O:37])[C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31].C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[Na+]>C(Cl)Cl.CN(C=O)C.CCOC(C)=O>[CH3:26][N:27]([C@@H:35]([CH3:59])[C:36]([NH:38][C@H:39]1[C@H:45]([CH3:46])[N:44]([C:47](=[O:53])[CH2:48][S:49]([CH3:52])(=[O:50])=[O:51])[C:43]2[CH:54]=[CH:55][CH:56]=[CH:57][C:42]=2[N:41]([CH2:12][C:11]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[N:4]=[CH:3][C:2]=2[CH3:1])[C:40]1=[O:58])=[O:37])[C:28](=[O:34])[O:29][C:30]([CH3:31])([CH3:32])[CH3:33]

Participants

10

Reactant 6

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 10796Cesium carbonateHCID 31297Methanesulfonyl chlorideHCID 14780591(3-Methylquinolin-4-yl)methanolHCID 90082560tert-butyl methyl((S)-1-((2S,3S)-2-methyl-1-(2-(methylsulfonyl)acetyl)-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl)carbamate

Product 1

HCID 90082413tert-butyl methyl((S)-1-((2S,3S)-2-methyl-5-((3-methylquinolin-4-yl)methyl)-1-(2-(methylsulfonyl)acetyl)-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl)carbamateYield 65%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a rt suspension of (3-methylquinolin-4-yl)methanol (90 mg, 520 μmol) in CH2Cl2 (5.2 ml) was added triethylamine (145 μl, 1.04 mmol), followed by methanesulfonyl chloride (48.4 μl, 624 μmol), dropwise. The reaction was stirred at rt for 2 h, then diluted with CH2Cl2, washed with H2O and sat. aq. NaCl, dried over Na2SO4, filtered, and concentrated. This material was mixed with tert-butyl methyl((S)-1-((2S,3S)-2-methyl-1-(2-(methylsulfonyl)acetyl)-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl)carbamate (167 mg, 336 μmol), cesium carbonate (142 mg, 437 μmol), and sodium iodide (65.5 mg, 437 μmol) in DMF (841 μl). The reaction was stirred at rt for 3.5 days, then diluted with EtOAc, washed with H2O and sat. aq. NaCl, dried over Na2SO4, filtered, and concentrated. The crude material was purified by flash chromatography to provide tert-butyl methyl((S)-1-((2S,3S)-2-methyl-5-((3-methylquinolin-4-yl)methyl)-1-(2-(methylsulfonyl)acetyl)-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl)carbamate (142 mg, 65%) as a white solid. MS m/z 652 (MH)+.

Workup

  1. washwashed with H2O and sat. aq. NaCl
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. stirringThe reaction was stirred at rt for 3.5 days
  6. washwashed with H2O and sat. aq. NaCl
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude material was purified by flash chromatography

Sources & evidence

ORD record
ord-7ffa473bd15742fd81fb8e5c06b22f62
Source dataset
uspto-grants-2016_08
Patent number
US09422331B2

Reaction notes

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