3-Aminobenzamide → HCID 11284996, compound

HRID 1391481Notes

Reaction equation

HRID 1391481 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:24])[C:10]2[CH:15]=[CH:14][C:13]([CH2:16][N:17]3[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]3)=[CH:12][CH:11]=2)=[CH:4][C:3]=1[NH:25][C:26]([N:28]1[C:32]2[N:33]=[CH:34][N:35]=[C:36](Cl)[C:31]=2[CH:30]=[CH:29]1)=[O:27].C(Cl)(=O)C.[NH2:42][C:43]1[CH:44]=[C:45]([CH:49]=[CH:50][CH:51]=1)[C:46]([NH2:48])=[O:47]>C(O)CCC>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:24])[C:10]2[CH:15]=[CH:14][C:13]([CH2:16][N:17]3[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]3)=[CH:12][CH:11]=2)=[CH:4][C:3]=1[NH:25][C:26]([N:28]1[C:32]2[N:33]=[CH:34][N:35]=[C:36]([NH:42][C:43]3[CH:51]=[CH:50][CH:49]=[C:45]([C:46](=[O:47])[NH2:48])[CH:44]=3)[C:31]=2[CH:30]=[CH:29]1)=[O:27]

Participants

5

Reactant 3

HCID 16453-AminobenzamideHCID 6367Acetyl chlorideHCID 11364360HCID 11364360, compound

Product 1

HCID 11284996HCID 11284996, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
80 °C

Procedure

4-Chloro-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid {2-methyl-5-[4-(4-methyl-piperazin-1-ylmethyl)-benzoylamino]-phenyl}-amide resin (50 mg, 0.05 mmol), prepared as in reference 2, in n-butanol (2 mL) is mixed with acetyl chloride (17.8 μL, 0.25 mmol) and 3-aminobenzamide (34 mg, 0.25 mmol), and shaken at 80° C. for 24 hours. The resulting mixture is filtered and the resin is treated with TFA/CH2Cl2/H2O (45/50/5) (600 μL) for 30 minutes before filtering and washing with CH2Cl2 (3×2 mL), MeOH (3×2 mL). The washes are then combined together and concentrated. The residue is purified by preparative HPLC-MS to give 4-(3-carbamoyl-phenylamino)-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid {2-methyl-5-[4-(4-methyl-piperazin-1-ylmethyl)-benzoylamino]-phenyl}-amide (18.5 mg, yield, 60%); 1H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 10.31 (s, 1H), 9.99 (s, 1H), 8.60 (s, 1H), 8.52 (d, J=1.71 Hz, 1H), 8.23 (s, 1H), 8.12 (d, J=7.59 Hz, 1H), 8.00 (s, 1H), 7.98 (d, J=8.02 Hz, 2H), 7.87 (d, J=3.89 Hz, 1H), 7.59 (dd, J=17.87, 9.00 Hz, 2H), 7.49 (d, J=7.98 Hz, 2H), 7.47 (s, 1H), 7.38 (s, 1H), 7.29 (d, J=8.48 Hz, 1H), 7.11 (d, J=3.89 Hz, 1H), 3.75 (s, 2H), 3.43-2.79 (m, 8H), 2.50 (s, 3H), 2.49 (s, 3H); ESIMS m/z 618.20 (M++1).

Workup

  1. filtrationThe resulting mixture is filtered
  2. additionthe resin is treated with TFA/CH2Cl2/H2O (45/50/5) (600 μL) for 30 minutes
  3. filtrationbefore filtering
  4. washwashing with CH2Cl2 (3×2 mL), MeOH (3×2 mL)
  5. concentrationconcentrated
  6. customThe residue is purified by preparative HPLC-MS

Sources & evidence

ORD record
ord-955d7bfc7da2498fb0a5df83ae41c0a2
Source dataset
uspto-grants-2008_03
Patent number
US07338957B2

Reaction notes

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