Methyl iodide → HCID 67696539, compound

HRID 343165Notes

Reaction equation

HRID 343165 reaction equation
[O:1]=[C:2]1[N:8]([CH2:9][C:10]([N:12]([CH:21]([CH3:23])[CH3:22])[C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)=[O:11])[C:7]2[CH:24]=[CH:25][CH:26]=[CH:27][C:6]=2[N:5]([C:28]2[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=2)[C:4](=[O:34])[CH2:3]1.[CH3:35][Si]([N-][Si](C)(C)C)(C)C.[Na+].CI.[NH4+].[Cl-]>CN(C=O)C.C1COCC1>[CH3:35][CH:3]1[C:2](=[O:1])[N:8]([CH2:9][C:10]([N:12]([CH:21]([CH3:23])[CH3:22])[C:13]2[CH:14]=[CH:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=2)=[O:11])[C:7]2[CH:24]=[CH:25][CH:26]=[CH:27][C:6]=2[N:5]([C:28]2[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=2)[C:4]1=[O:34]

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 25517Ammonium ChlorideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 67611178HCID 67611178, compound

Product 1

HCID 67696539HCID 67696539, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of 2.65 g (5.78 mmol) of 2-(2,4-Dioxo-5-pyridin-3-yl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl) acetamide in 80 mL of DMF at 0° C. is added 6.36 mL (6.36 mmol) of a 1.0M solution of NaN(TMS)2 in THF. The resulting solution is stirred 10 min, then 400 mL (6.36 mmol) of methyl iodide is added neat. The resulting solution is stirred at RT for 45 min then poured into 100 mL NH4Cl. The reaction mixture is concentrated to remove the DMF, diluted with 500 mL of H2O and extracted with EtOAc (3×200 mL). The organics were dried (MgSO4), and the solvents removed in vacuo. Purification by silica gel flash chromatography using EtOAc as eluent afforded 2.52 g of 2-(3-Methyl-2,4-dioxo-5-pyridin-3-yl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl)-acetamide as a white foam: 1H NMR (CDCl3, 400 MHz) δ8.50 (s, br, 2H), 7.79 (d, 1H, J=8.1), 7.43 (d, 1H, J=8.1), 7.36-6.94 (m, 8H), 6.88 (d, 1H, J=8.8), 4.98 (m, 1H), 4.26 (m, 2H), 3.85 (s, 3H), 3.54 (q, 1H, J=7.1), 1.42 (d, 3H, J=7.1), 1.07 (m, 6H); low resolution MS (FAB)m/e 473 (MH+); Anal. (C27H28N4O4) Calcd. C, 68.63; H, 5.97; N, 11.86 Found C, 66.91; H, 6.13; N, 11.29.

Workup

  1. stirringThe resulting solution is stirred at RT for 45 min
  2. concentrationThe reaction mixture is concentrated
  3. customto remove the DMF
  4. additiondiluted with 500 mL of H2O
  5. extractionextracted with EtOAc (3×200 mL)
  6. dry with materialThe organics were dried (MgSO4)
  7. customthe solvents removed in vacuo
  8. customPurification by silica gel flash chromatography

Sources & evidence

ORD record
ord-e039d2747d034388a8a60517917b9835
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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