Sodium Iodide → tert-butyl(S)-1-((3S,4S)-1-((2-methoxynaphthalen-1-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

HRID 1486044Notes

Reaction equation

HRID 1486044 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].Cl[CH2:37][C:38]1[C:47]2[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=2)[CH:41]=[CH:40][C:39]=1[O:48][CH3:49].C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[Na+]>CN(C)C=O.C(OCC)(=O)C>[CH3:49][O:48][C:39]1[CH:40]=[CH:41][C:42]2[C:47](=[CH:46][CH:45]=[CH:44][CH:43]=2)[C:38]=1[CH2:37][N:16]1[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]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]1=2

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 133566461-(Chloromethyl)-2-methoxynaphthaleneHCID 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 118292636tert-butyl(S)-1-((3S,4S)-1-((2-methoxynaphthalen-1-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)carbamateYield 52.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a room temperature 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 (prepared as in Example RK-1, Step 3, 75 mg, 154 μmol) in N,N-dimethylformamide (500 μl) was added 1-(chloromethyl)-2-methoxynaphthalene (38 mg, 184 μmol), cesium carbonate (65 mg, 200 μmol), and sodium iodide (30 mg, 200 μmol). The reaction was stirred at room temperature for 16 h. After this time, the reaction mixture was diluted with ethyl acetate (20 mL), washed with water (20 mL) the aqueous layer was then extracted with ethyl acetate (2×20 mL) and the organic layers combined and then washed with a saturated aqueous sodium chloride solution (30 mL), dried over magnesium sulfate, filtered, and the filterate concentrated in vacuo. The crude material was purified by flash chromatography to afford tert-butyl(S)-1-((3S,4S)-1-((2-methoxynaphthalen-1-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 (53 mg, 52%) as a light yellow foam: LC-MS m/z 681 [M+Na]+.

Workup

  1. customTo a room temperature
  2. washwashed with water (20 mL) the aqueous layer
  3. extractionwas then extracted with ethyl acetate (2×20 mL)
  4. washwashed with a saturated aqueous sodium chloride solution (30 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationthe filterate concentrated in vacuo
  8. customThe crude material was purified by flash chromatography

Sources & evidence

ORD record
ord-3f1f5a0468cf4b68bc3939b9ceb39967
Source dataset
uspto-grants-2016_08
Patent number
US09422331B2

Reaction notes

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