Chloro-N,N-diethylacetamide → HCID 89761686, compound

HRID 528620Notes

Reaction equation

HRID 528620 reaction equation
COC1C=CC(C[N:8]([C:22]2[S:23][CH:24]=[CH:25][N:26]=2)[S:9]([C:12]2[CH:13]=[CH:14][C:15]3[NH:20][CH2:19][CH2:18][O:17][C:16]=3[CH:21]=2)(=[O:11])=[O:10])=CC=1.[H-].[Na+].Cl[CH2:32][C:33]([N:35]([CH2:38][CH3:39])[CH2:36][CH3:37])=[O:34]>CN(C=O)C>[CH2:36]([N:35]([CH2:38][CH3:39])[C:33](=[O:34])[CH2:32][N:20]1[CH2:19][CH2:18][O:17][C:16]2[CH:21]=[C:12]([S:9](=[O:10])(=[O:11])[NH:8][C:22]3[S:23][CH:24]=[CH:25][N:26]=3)[CH:13]=[CH:14][C:15]1=2)[CH3:37]

Participants

5

Reactant 3

HCID 16844Chloro-N,N-diethylacetamideHCID 24758Sodium hydrideHCID 89761436N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide2×

Product 1

HCID 89761686HCID 89761686, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a flask charged with N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (INTERMEDIate M) (0.104 g, 0.25 mmol) was added DMF (0.7 ml), and cooled in an ice water bath prior to the addition of NaH (60% in mineral oil) (10 mg, 0.25 mmol). The mixture was stirred for 45 min at 0° C., then 30 min at room temperature. To a separate vial charged with 2-chloro-N,N-diethylacetamide (37 mg, 0.25 mmol) was added DMF (0.3 ml), then the solution of deprotonated amine. The resulting mixture was sealed and shaken at rt overnight. The mixture was quenched with the addition of MeOH, then dried under reduced pressure and purified with NH4OH modified RP-HPLC affording N,N-diethyl-2-(7-(N-(thiazol-2-yl)sulfamoyl)-2H-benzo[b][1,4]oxazin-4(3 H)-yl)acetamide (27.4 mg, 27%). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.01 (t, J=7.05 Hz, 3 H) 1.18 (t, J=7.10 Hz, 3 H) 3.21-3.27 (m, 2 H) 3.36 (br. s., 2 H) 3.39-3.45 (m, 2 H) 4.18 (t, J=4.35 Hz, 2 H) 4.26 (s, 2 H) 6.49 (d, J=8.71 Hz, 1 H) 6.75 (d, J=4.35 Hz, 1 H) 7.00 (d, J=2.06 Hz, 1 H) 7.13 (dd, J=8.59, 2.06 Hz, 1 H) 7.19 (d, J=4.58 Hz, 1 H) 12.47 (br. s., 1 H). m/z (ESI) 411.1 (M+H)+.

Workup

  1. temperaturecooled in an ice water bath
  2. custom30 min
  3. customat room temperature
  4. customThe resulting mixture was sealed
  5. stirringshaken at rt overnight
  6. customThe mixture was quenched with the addition of MeOH
  7. customdried under reduced pressure
  8. custompurified with NH4OH modified RP-HPLC

Sources & evidence

ORD record
ord-dbac23b9565c4fa9ab1f27a0b1d18ccf
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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