P-Anisidine → HCID 59851797, compound

HRID 2373438Notes

Reaction equation

HRID 2373438 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:11]3[N:12]=[C:13]([NH:16][C:17]4[CH:25]=[CH:24][C:20]([C:21](O)=[O:22])=[CH:19][CH:18]=4)[N:14]=[CH:15][C:10]=3[CH2:9][C:8](=[O:26])[NH:7][C:6]=2[CH:27]=1.ClC(Cl)(Cl)C#N.C(N(CC)CC)C.[CH3:41][O:42][C:43]1[CH:48]=[CH:47][C:46]([NH2:49])=[CH:45][CH:44]=1>CC(N(C)C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:11]3[N:12]=[C:13]([NH:16][C:17]4[CH:18]=[CH:19][C:20]([C:21]([NH:49][C:46]5[CH:47]=[CH:48][C:43]([O:42][CH3:41])=[CH:44][CH:45]=5)=[O:22])=[CH:24][CH:25]=4)[N:14]=[CH:15][C:10]=3[CH2:9][C:8](=[O:26])[NH:7][C:6]=2[CH:27]=1

Participants

6

Reactant 4

HCID 7732P-AnisidineHCID 8471TriethylamineHCID 11011TrichloroacetonitrileHCID 56946587HCID 56946587, compound

Product 1

HCID 59851797HCID 59851797, compound

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Procedure

To a pre swelled PL-TPP resin [200 mg, 0.3 mmol, (Polymer labs, 1.5 mmol/gram loading)] in DMA (1.0 mL) was added a mixture of 4-(9-Chloro-6-oxo-6,7-dihydro-5H-benzo[b]pyrimido[4,5-d]azepin-2-ylamino)-benzoic acid (I-3) (25 mg 0.066 mmol), DMA (1.5 mL) and trichloroacetonitrile (0.53 mmol). After agitating for three hours at room temperature, triethylamine (46 μL, 0.33 mmol) was added, followed by p-anisidine (8.1 mg, 0.066 mmol). The reaction mixture was stirred at 22° C. overnight. The reaction mixture was filtered and the resin was washed with DMF, DMA, and MeOH (1×1 mL). The combined organic layers were concentrated and the crude product was purified by RP-HPLC using an Agilent HPLC equipped with a SunFire™ column (Waters Corporation), Method Formic Acid, to give I-555 (22 mg, 69%). 1H NMR (DMSO): δ 10.38 (s, 1H), 10.32 (s, 1H), 9.93 (s, 1H), 8.59 (s, 1H), 8.10(d, J=8.9 Hz, 1H), 7.92 (s, 1H), 7.64 (d, J=9.3 Hz, 1H), 7.42 (d, J=8.1 Hz, 1H), 7.29 (s, 1H), 6.89 9d, J=8.5 Hz, 1H), 3.73 (s, 2H), 3.43 (s, 1H), 3.32 (s, 3H); MS Rt═2.70 min (m/z) 466 (M+1),

Workup

  1. additionwas added
  2. stirringThe reaction mixture was stirred at 22° C. overnight
  3. filtrationThe reaction mixture was filtered
  4. washthe resin was washed with DMF, DMA, and MeOH (1×1 mL)
  5. concentrationThe combined organic layers were concentrated
  6. customthe crude product was purified by RP-HPLC
  7. customequipped with a SunFire™ column (Waters Corporation), Method Formic Acid
  8. customto give I-555 (22 mg, 69%)

Sources & evidence

ORD record
ord-8743b014c84f486d850c70c341734e1b
Source dataset
uspto-grants-2008_12
Patent number
US07459448B2

Reaction notes

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