Sodium Iodide → tert-butyl(S)-1-((3S,4S)-1-((3-cyclopropylquinolin-4-yl)methyl)-4-methyl-2-oxo-5-(tetrahydro-2H-pyran-4-carbonyl)-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-ox opropan-2-yl(methyl)carbamate

HRID 1486070Notes

Reaction equation

HRID 1486070 reaction equation
[CH3:1][N:2]([C@@H:10]([CH3:35])[C:11]([NH:13][C@H:14]1[C@H:20]([CH3:21])[N:19]([C:22]([CH:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)=[O:23])[C:18]2[CH:30]=[CH:31][CH:32]=[CH:33][C:17]=2[NH:16][C:15]1=[O:34])=[O:12])[C:3](=[O:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6].CS(O[CH2:41][C:42]1[C:51]2[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=2)[N:45]=[CH:44][C:43]=1[CH:52]1[CH2:54][CH2:53]1)(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[Na+]>CN(C=O)C.CCOC(C)=O>[CH:52]1([C:43]2[CH:44]=[N:45][C:46]3[C:51]([C:42]=2[CH2:41][N:16]2[C:15](=[O:34])[C@@H:14]([NH:13][C:11](=[O:12])[C@@H:10]([N:2]([CH3:1])[C:3](=[O:9])[O:4][C:5]([CH3:6])([CH3:7])[CH3:8])[CH3:35])[C@H:20]([CH3:21])[N:19]([C:22]([CH:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[O:23])[C:18]4[CH:30]=[CH:31][CH:32]=[CH:33][C:17]2=4)=[CH:50][CH:49]=[CH:48][CH:47]=3)[CH2:54][CH2:53]1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 89922492(3-Cyclopropylquinolin-4-yl)methyl methanesulfonateHCID 90082481tert-butyl methyl((S)-1-((2S,3S)-2-methyl-4-oxo-1-(tetrahydro-2H-pyran-4-carbonyl)-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl)carbamate

Product 1

HCID 118292684tert-butyl(S)-1-((3S,4S)-1-((3-cyclopropylquinolin-4-yl)methyl)-4-methyl-2-oxo-5-(tetrahydro-2H-pyran-4-carbonyl)-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-ox opropan-2-yl(methyl)carbamateYield 52%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a rt solution of tert-butyl methyl((S)-1-((2S,3S)-2-methyl-4-oxo-1-(tetrahydro-2H-pyran-4-carbonyl)-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl)carbamate (110 mg, 225 μmol) in DMF (563 μl) was added (3-cyclopropylquinolin-4-yl)methyl methanesulfonate (74.9 mg, 270 μmol), cesium carbonate (95.4 mg, 293 μmol), and sodium iodide (43.9 mg, 293 μmol). The reaction was stirred at rt for 2.5 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(S)-1-((3S,4S)-1-((3-cyclopropylquinolin-4-yl)methyl)-4-methyl-2-oxo-5-(tetrahydro-2H-pyran-4-carbonyl)-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (78 mg, 52%) as an off-white solid. MS m/z 670 (MH)+.

Workup

  1. washwashed with H2O and sat. aq. NaCl
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude material was purified by flash chromatography

Sources & evidence

ORD record
ord-a556787be5554880acadee0ff9a36d25
Source dataset
uspto-grants-2016_08
Patent number
US09422331B2

Reaction notes

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