Diisopropylcarbodiimide → N-{(4-Fluoro-phenyl)-[2-(4-methoxy-phenylamino)-ethylcarbamoyl]-methyl}-3-methyl-benzamide

HRID 2215628Notes

Reaction equation

HRID 2215628 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:12][C:13](=[O:21])[C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[CH:15]=2)[C:9]([OH:11])=O)=[CH:4][CH:3]=1.C1C=CC2N(O)N=NC=2C=1.CC(C)N=C=NC(C)C.[CH3:41][O:42][C:43]1[CH:48]=[CH:47][C:46]([NH:49][CH2:50][CH2:51][NH2:52])=[CH:45][CH:44]=1>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([C:9](=[O:11])[NH:52][CH2:51][CH2:50][NH:49][C:46]2[CH:47]=[CH:48][C:43]([O:42][CH3:41])=[CH:44][CH:45]=2)[NH:12][C:13](=[O:21])[C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[CH:15]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 12666396N~1~-(4-Methoxyphenyl)ethane-1,2-diamineHCID 21950688(4-Fluoro-phenyl)-(3-methyl-benzoylamino)-acetic acid

Product 1

HCID 21055513N-{(4-Fluoro-phenyl)-[2-(4-methoxy-phenylamino)-ethylcarbamoyl]-methyl}-3-methyl-benzamideYield 36%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-Fluoro-phenyl glycine 1 (20 mg, 0.12 mmol) was dissolved in H2O (1 mL) containing equimolar amounts of NaOH (5 mg, 0.12 mmol). The solution was cooled to 0° C., then m-toluoyl chloride (16 μL, 0.12 mmol) was added dropwise under vigorous stirring. The mixture was allowed to warm to room temperature and stirred for approx. 12 h. After acidification with 1 M HCl (1 mL), the product was extracted from the reaction mixture with DCM (4 mL). The organic layer was separated and the solvent was removed in vacuo to yield (4-Fluoro-phenyl)-(3-methyl-benzoylamino)-acetic acid 2 (34 mg, 0.12 mmol, quant.) as a white solid: 1H-NMR (400 MHz, CD3OD) δ=7.67–7.08 (m, 8H), 5.66 (s, 1H), 2.38 (s, 3H). MS calcd. for C16H15FNO3 (M+H+) 288.10. found 288.4. Step B: (4-Fluoro-phenyl)-(3-methyl-benzoylamino)-acetic acid 2 (34 mg, 0.12 mmol) was dissolved in DCM (2 mL), HOBt (20 mg, 0.14 mmol) and DIC (23 μL, 0.14 mmol) were added and the solution was stirred for 10 min at room temperature. N-(4-Methoxyphenyl)-ethane-1,2-diamine (24 mg, 0.14 mmol) was added and the solution was stirred for 3 h at room temperature. The solvent was removed in vacuo, and the remainder was purified by reverse HPLC to afford N-{(4-Fluoro-phenyl)-[2-(4-methoxy-phenylamino)-ethylcarbamoyl]-methyl}-3-methyl-benzamide 3 (19 mg, 0.04 mmol, 36%) as a white solid:

Workup

  1. stirringthe solution was stirred for 3 h at room temperature
  2. customThe solvent was removed in vacuo
  3. customthe remainder was purified by reverse HPLC

Sources & evidence

ORD record
ord-e212809d885b45e3a523203608228c9a
Source dataset
uspto-grants-2006_09
Patent number
US07109243B2

Reaction notes

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