4-(Chloromethyl)benzoyl chloride → Tert-butyl 4-(4-{[4-carbamoyl-2-(naphthalen-2-ylamino)thiazol-5-yl]carbamoyl}benzyl)piperazine-1-carboxylate

HRID 512533Notes

Reaction equation

HRID 512533 reaction equation
[NH2:1][C:2]1[S:6][C:5]([NH:7][C:8]2[CH:17]=[CH:16][C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH:9]=2)=[N:4][C:3]=1[C:18]([NH2:20])=[O:19].C(N(CC)C(C)C)(C)C.Cl[CH2:31][C:32]1[CH:40]=[CH:39][C:35]([C:36](Cl)=[O:37])=[CH:34][CH:33]=1.[C:41]([N:48]1[CH2:53][CH2:52][NH:51][CH2:50][CH2:49]1)([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42]>CC(N(C)C)=O.C(OCC)(=O)C>[C:18]([C:3]1[N:4]=[C:5]([NH:7][C:8]2[CH:17]=[CH:16][C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH:9]=2)[S:6][C:2]=1[NH:1][C:36]([C:35]1[CH:39]=[CH:40][C:32]([CH2:31][N:51]2[CH2:50][CH2:49][N:48]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:53][CH2:52]2)=[CH:33][CH:34]=1)=[O:37])(=[O:19])[NH2:20]

Participants

7

Reactant 4

HCID 701364-(Chloromethyl)benzoyl chlorideHCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 867033695-Amino-2-(naphthalen-2-ylamino)thiazole-4-carboxamide

Product 1

HCID 86703373Tert-butyl 4-(4-{[4-carbamoyl-2-(naphthalen-2-ylamino)thiazol-5-yl]carbamoyl}benzyl)piperazine-1-carboxylateYield 11%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent2×

Procedure

To a mixture of 5-amino-2-(naphthalen-2-ylamino)thiazole-4-carboxamide (0.5 g, 1.76 mmol) and N,N-diisopropylethylamine (0.3 mL, 1.94 mmol) in DMA (30 mL) was added 4-chloromethylbenzoyl chloride (0.37g, 1.94 mmol) at 0° C. The mixture was stirred for 3 hrs at rt. Then 1-Boc-piperazine (0.18 g, 0.95 mmol) was added to the mixture (0.083 g in 5 mL DMA), and the mixture was stirred for 16 hrs at rt. The reaction mixture was diluted with ethyl acetate (150 mL), washed with water, and dried over Na2SO4. The solvent was evaporated under reduced pressure, and the crude residue was purified by silica gel column chromatography eluted with 5% MeOH in DCM to give 0.010 g (11% yield) of the titled compound.

Workup

  1. stirringthe mixture was stirred for 16 hrs at rt
  2. washwashed with water
  3. dry with materialdried over Na2SO4
  4. customThe solvent was evaporated under reduced pressure
  5. customthe crude residue was purified by silica gel column chromatography
  6. washeluted with 5% MeOH in DCM

Sources & evidence

ORD record
ord-d53f941e873b4db3a8df1cf1f36a4c4f
Source dataset
uspto-grants-2015_08
Patent number
US09102637B2

Reaction notes

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