Sodium bis(trimethylsilyl)amide → HCID 67699907, compound

HRID 343220Notes

Reaction equation

HRID 343220 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:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:4](=[O:34])[CH2:3]1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Br[CH2:46][C:47]1[C:55]2[C:50](=[N:51][CH:52]=[CH:53][CH:54]=2)[O:49][N:48]=1>CN(C=O)C.C1COCC1>[CH:21]([N:12]([C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=1)[C:10](=[O:11])[CH2:9][N:8]1[C:2](=[O:1])[CH:3]([CH2:46][C:47]2[C:55]3[C:50](=[N:51][CH:52]=[CH:53][CH:54]=3)[O:49][N:48]=2)[C:4](=[O:34])[N:5]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[C:6]2[CH:27]=[CH:26][CH:25]=[CH:24][C:7]1=2)([CH3:23])[CH3:22]

Participants

6

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 107900232-(2,4-Dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl) acetamideHCID 122560533-(bromomethyl)isoxazolo[5,4-b]pyridine

Product 1

HCID 67699907HCID 67699907, compoundYield 71.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of 300 mg (0.66 mmol) of 2-(2,4-Dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl) acetamide, prepared as in Intermediate 4, in 8 mL of DMF at 0° C. is added 0.78 mL (0.78 mmol, 1.2 equiv) of a 1.0M solution of NaN(TMS)2 in THF. The resulting solution is stirred 5 min, and a solution of 154 mg (0.972 mmol, 1.1 equiv.) of 3-bromomethyl isoxazolo[5,4-b]pyridine (Abignente, A.; De Capraris, P.; Stein, M. L. Farmaco Ed. Sci. 1975, 30, 992) in 2 mL of DMF is added. The resulting solution is stirred for 2.5 h at RT then quenched with 5 mL of H2O. The reaction mixture is poured into 50 mL of EtOAc and extracted with H2O (2×50 mL). The organic layer is separated, dried (MgSO4), and the solvents removed in vacuo. Purification by silica gel MPLC using an Si60 column and hexane/EtOAc 1/1 as eluent afforded 280 mg of the title compound as a white amorphous solid: 1H NMR (CDCl3, 400 MHz) δ8.57 (dd, 1H, J=1.5, 4.6), 8.23 (dd, 1H, J=1.5, 7.8), 7.39-7.10 (m, 12H), 6.94 (m, 2H), 4.99 (m, 1H), 4.23 (m, 3H), 3.84 (s, 3H), 3.79 (d 1H, J=8.4), 3.57 (dd, 1H, J=5.3, 16.4), 1.06 (d, 6H, J=6.8); low resolution MS (FAB)m/e 590 (MH+), 589 (M+), 425; Anal. (C34H31N5O5) Calcd. C, 69.26; H, 5.30; N, 11.88 Found C, 69.13; H, 5.32; N, 11.84.

Workup

  1. stirringThe resulting solution is stirred for 2.5 h at RT
  2. customthen quenched with 5 mL of H2O
  3. additionThe reaction mixture is poured into 50 mL of EtOAc
  4. extractionextracted with H2O (2×50 mL)
  5. customThe organic layer is separated
  6. dry with materialdried (MgSO4)
  7. customthe solvents removed in vacuo
  8. customPurification by silica gel MPLC

Sources & evidence

ORD record
ord-0f1fe01dbab14491bc9ed26e25e8c4e3
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

Loading…