Trifluoroacetic acid → HCID 25057150, compound

HRID 418323Notes

Reaction equation

HRID 418323 reaction equation
C(OC([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:18](=[O:39])[NH:19][C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([CH2:26][NH:27][C:28]([NH:30][C:31]4[CH:36]=[CH:35][C:34]([C:37]#[N:38])=[CH:33][CH:32]=4)=[O:29])[CH:21]=3)[CH:14]=2)[CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>ClCCl>[C:37]([C:34]1[CH:35]=[CH:36][C:31]([NH:30][C:28](=[O:29])[NH:27][CH2:26][C:22]2[CH:21]=[C:20]([NH:19][C:18]([C:13]3[CH:14]=[C:15]4[C:10](=[CH:11][CH:12]=3)[CH2:9][NH:8][CH2:17][CH2:16]4)=[O:39])[CH:25]=[CH:24][CH:23]=2)=[CH:32][CH:33]=1)#[N:38]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59190885HCID 59190885, compound

Product 1

HCID 25057150HCID 25057150, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3,4-Dihydro-1H-isoquinoline-2,6-dicarboxylic acid 2-tert-butyl ester (50 mg, 0.18 mmol), EDC (38.3 mg, 0.2 mmol) and HOBt (24.3 mg, 0.18 mmol) were combined in a reaction vial, and DMF (1 mL) was added. To the solution thus formed, N-methylmorpholine (0.22 mL, 0.2 mmol) was added and the reaction mixture was agitated for 1 hour. The urea, 1-(3-amino-benzyl)-3-(4-cyano-phenyl)-urea (40 mg, 0.15 mmol), prepared as described above, was then added as a solution in DMF (0.3 mL), and the reaction mixture was agitated for 48 h. The reaction mixture was diluted to 6 mL with dichloromethane, washed with 1N HCl (3×2 mL), NaHCO3 (satd. aq., 3×2 mL, and brine (1×2 mL), dried and evaporated to 59 mg of an oil (95% yield). This intermediate (6-{3-[3-(4-cyano-phenyl)-ureidomethyl]-phenylcarbamoyl}-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester) was dissolved in dichloromethane (1 mL) and TFA (0.4 mL) was added. The reaction mixture was stirred for 2 h, then the solvents were evaporated and the resulting residue was purified directly by preparative HPLC using an acetonitrile/water/formic acid gradient providing the title compound (20 mg, 48% yield), MS analysis electrospray, 426 (M+H).

Workup

  1. customthe solvents were evaporated
  2. customthe resulting residue was purified directly by preparative HPLC

Sources & evidence

ORD record
ord-382fc2e8f289483690a37f129007bd6d
Source dataset
uspto-grants-2012_01
Patent number
US08093266B2

Reaction notes

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