Triethylamine → HCID 69210349, compound

HRID 131145Notes

Reaction equation

HRID 131145 reaction equation
[CH3:1][N:2]([CH3:14])[C:3]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][CH:6]=1)=[O:4].S(Cl)(Cl)=O.[NH2:19][C@H:20]1[CH2:25][C:24]2[C:26]([N:30]3[CH2:35][CH2:34][N:33]([CH3:36])[CH2:32][CH2:31]3)=[CH:27][CH:28]=[CH:29][C:23]=2[O:22][CH2:21]1.C(N(CC)CC)C>C(Cl)Cl>[CH3:36][N:33]1[CH2:34][CH2:35][N:30]([C:26]2[C:24]3[CH2:25][C@H:20]([NH:19][C:9](=[O:11])[C:8]4[CH:7]=[CH:6][C:5]([C:3]([N:2]([CH3:1])[CH3:14])=[O:4])=[CH:13][CH:12]=4)[CH2:21][O:22][C:23]=3[CH:29]=[CH:28][CH:27]=2)[CH2:31][CH2:32]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 110954804-(Dimethylcarbamoyl)benzoic acidHCID 11139461(S)-3-amino-5-(4-methylpiperazin-1-yl)-1,4-dihydro-2H-1-benzopyran

Product 1

HCID 69210349HCID 69210349, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 4-(N,N-dimethylaminocarbonyl)benzoic acid (110 mg, 0.56 mmol; described in: U.S. Pat. No. 3,607,918, 1971) was dropwise added thionyl chloride (500 μL, 6.9 mmol). The reaction mixture was stirred at ambient temperature for 1 min and then concentrated in vacuo. The excess of thionyl chloride was co-evaporated with toluene in vacuo. The crude acid chloride was dissolved in methylene chloride (8 mL) and dropwise added to a solution of (S)-3-amino-5-(4-methylpiperazin-1-yl)-3,4 dihydro-2H-1-benzopyran (130 mg, 0.53 mmol) and triethylamine (110 μL, 0.80 mmol) in methylene chloride (5 mL) at 0° C. The reaction mixture was stirred at 0° C. for 30 min and at room temperature for an additional 30 min. The solvent was evaporated in vacuo giving 300 mg of a crude product. Purification by preparative TLC on silica using chloroform/ethanol (saturated with ammonia) 10:1 as the eluent afforded 120 mg (54% yield) of the title compound as a white solid: mp 219° C. (dec); EIMS (70 eV) m/z (relative intensity) 422 (47, M+); [α]22D −12° (c 0.42, chloroform).

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe crude acid chloride was dissolved in methylene chloride (8 mL)
  3. stirringThe reaction mixture was stirred at 0° C. for 30 min and at room temperature for an additional 30 min
  4. customThe solvent was evaporated in vacuo
  5. customgiving 300 mg of a crude product
  6. customPurification by preparative TLC on silica

Sources & evidence

ORD record
ord-ef697e4d26184095ab3651341663a7dd
Source dataset
uspto-grants-2008_06
Patent number
US07384943B2

Reaction notes

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