Triethylamine → HCID 58349067, compound

HRID 2190396Notes

Reaction equation

HRID 2190396 reaction equation
[NH2:1][C:2]1[S:3][C:4]2[CH:10]=[C:9]([O:11][C:12]3[CH:13]=[C:14]([NH:18][C:19](=[O:31])[C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([C:29]#[N:30])([CH3:28])[CH3:27])[CH:21]=4)[CH:15]=[CH:16][CH:17]=3)[CH:8]=[CH:7][C:5]=2[N:6]=1.Cl.Cl.[CH3:34][N:35]1[CH2:40][CH2:39][N:38]([CH2:41][C:42](O)=[O:43])[CH2:37][CH2:36]1.C(N(CC)CC)C.Cl.C(N=C=NCCCN(C)C)C>N1C=CC=CC=1.CN(C)C1C=CN=CC=1.CO>[C:29]([C:26]([C:22]1[CH:21]=[C:20]([CH:25]=[CH:24][CH:23]=1)[C:19]([NH:18][C:14]1[CH:15]=[CH:16][CH:17]=[C:12]([O:11][C:9]2[CH:8]=[CH:7][C:5]3[N:6]=[C:2]([NH:1][C:42](=[O:43])[CH2:41][N:38]4[CH2:39][CH2:40][N:35]([CH3:34])[CH2:36][CH2:37]4)[S:3][C:4]=3[CH:10]=2)[CH:13]=1)=[O:31])([CH3:27])[CH3:28])#[N:30]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 448914242-(4-Methylpiperazin-1-yl)acetic acid dihydrochlorideHCID 57387331N-{3-[(2-amino-1,3-benzothiazol-6-yl)oxy]phenyl}-3-(1-cyano-1-methylethyl)benzamide

Product 1

HCID 58349067HCID 58349067, compoundYield 29%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalyst2×HCID 887MethanolSolventHCID 1049PyridineSolvent

Procedure

To a solution of N-{3-[(2-amino-1,3-benzothiazol-6-yl)oxy]phenyl}-3-(1-cyano-1-methylethyl)benzamide (452 mg, 1.05 mmol) produced in Example A12(iv) in pyridine (10 mL) were added (4-methylpiperazin-1-yl)acetic acid dihydrochloride (273 mg, 1.18 mmol), N,N-dimethylpyridine-4-amine (89.1 mg, 729 μmol), triethylamine (10 mL) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (492 mg, 2.57 mmol) at room temperature, and the mixture was stirred for 14 hr. To the reaction mixture were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (483 mg, 2.52 mmol) and N,N-dimethylpyridine-4-amine (292 mg, 2.39 mmol) and the mixture was further stirred for 4 hr. To the reaction mixture was added methanol (10 mL), and the mixture was stirred at room temperature for 30 min, and concentrated under reduced pressure. The residue was diluted with ethyl acetate (100 mL), washed with saturated aqueous ammonium chloride solution (50 mL×2) and saturated aqueous sodium hydrogencarbonate solution (50 mL), successively, and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=80/20→20/80) and triturated with ethyl acetate and diisopropyl ether to give the title compound (171 mg, 29%) as a colorless solid.

Workup

  1. stirringthe mixture was further stirred for 4 hr
  2. stirringthe mixture was stirred at room temperature for 30 min
  3. concentrationconcentrated under reduced pressure
  4. additionThe residue was diluted with ethyl acetate (100 mL)
  5. washwashed with saturated aqueous ammonium chloride solution (50 mL×2) and saturated aqueous sodium hydrogencarbonate solution (50 mL)
  6. dry with materialsuccessively, and dried over anhydrous magnesium sulfate
  7. filtrationThe insoluble material was filtered off
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=80/20→20/80)
  10. customtriturated with ethyl acetate and diisopropyl ether

Sources & evidence

ORD record
ord-3a082dc3f6334300abd675a758df7c45
Source dataset
uspto-grants-2012_12
Patent number
US08324395B2

Reaction notes

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