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

HRID 1486055Notes

Reaction equation

HRID 1486055 reaction equation
[Cl:1][C:2]1[C:11]([CH3:12])=[C:10]([CH2:13]O)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.[CH3:27][N:28]([C@@H:36]([CH3:60])[C:37]([NH:39][C@H:40]1[C@H:46]([CH3:47])[N:45]([C:48](=[O:54])[CH2:49][S:50]([CH3:53])(=[O:52])=[O:51])[C:44]2[CH:55]=[CH:56][CH:57]=[CH:58][C:43]=2[NH:42][C:41]1=[O:59])=[O:38])[C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32].C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[Na+]>C(Cl)Cl.CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[C:11]([CH3:12])=[C:10]([CH2:13][N:42]2[C:41](=[O:59])[C@@H:40]([NH:39][C:37](=[O:38])[C@@H:36]([N:28]([CH3:27])[C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:32])[CH3:33])[CH3:60])[C@H:46]([CH3:47])[N:45]([C:48](=[O:54])[CH2:49][S:50]([CH3:53])(=[O:52])=[O:51])[C:44]3[CH:55]=[CH:56][CH:57]=[CH:58][C:43]2=3)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1

Participants

10

Reactant 6

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 10796Cesium carbonateHCID 31297Methanesulfonyl chlorideHCID 89923521(2-Chloro-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 118292663tert-butyl(S)-1-((3S,4S)-1-((2-chloro-3-methylquinolin-4-yl)methyl)-4-methyl-5-(2-(methylsulfonyl)acetyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamateYield 45.4%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a rt suspension of (2-chloro-3-methylquinolin-4-yl)methanol (61 mg, 294 μmol) in CH2Cl2 (2.94 ml) was added triethylamine (81.9 μl, 588 μmol), followed by methanesulfonyl chloride (27.3 μl, 353 μmol), dropwise. The reaction was stirred at rt for 1.5 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 (100 mg, 201 μmol), cesium carbonate (85.3 mg, 262 μmol), and sodium iodide (39.2 mg, 262 μmol) in DMF (503 μl). The reaction was stirred at rt for 16 h, 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(S)-1-((3S,4S)-1-((2-chloro-3-methylquinolin-4-yl)methyl)-4-methyl-5-(2-(methylsulfonyl)acetyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (62.6 mg, 45%) as a white solid. MS m/z 708 (MNa)+.

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 16 h
  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-18acdcd93776476ab207ced07b242373
Source dataset
uspto-grants-2016_08
Patent number
US09422331B2

Reaction notes

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