Hydrochloric Acid → HCID 11296366, compound

HRID 1391479Notes

Reaction equation

HRID 1391479 reaction equation
[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([C:16]3[CH:17]=[C:18]([NH:22][C:23]([N:25]4[C:29]5[N:30]=[CH:31][N:32]=[C:33](Cl)[C:28]=5[CH:27]=[CH:26]4)=[O:24])[CH:19]=[CH:20][CH:21]=3)=[O:15])=[CH:9][CH:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(Cl)(=O)C.[F:39][C:40]([F:49])([F:48])[C:41]1[CH:42]=[C:43]([CH:45]=[CH:46][CH:47]=1)[NH2:44].Cl>C(O)CCC>[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([C:16]3[CH:17]=[C:18]([NH:22][C:23]([N:25]4[C:29]5[N:30]=[CH:31][N:32]=[C:33]([NH:44][C:43]6[CH:45]=[CH:46][CH:47]=[C:41]([C:40]([F:39])([F:48])[F:49])[CH:42]=6)[C:28]=5[CH:27]=[CH:26]4)=[O:24])[CH:19]=[CH:20][CH:21]=3)=[O:15])=[CH:9][CH:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6367Acetyl chlorideHCID 73753-(Trifluoromethyl)aniline2×HCID 86619979HCID 86619979, compound

Product 1

HCID 11296366HCID 11296366, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
80 °C

Procedure

4-Chloro-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid [3-(4-morpholin-4-yl-phenylcarbamoyl)-phenyl]-amide resin(50 mg, 0.05 mmol), prepared as in reference 1, in n-butanol (2 mL) is mixed with acetyl chloride (17.8 μL, 0.25 mmol) and 3-trifluoromethyl-aniline (31 μL, 0.25 mmol), or only mixed with HCl salt of 3-trifluoromethyl-aniline (50 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 to give 4-(3-trifluoromethyl-phenylamino)-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid [3-(4-morpholin-4-yl-phenylcarbamoyl)-phenyl]-amide (19.0 mg, yield 64%). 1H NMR (400 MHz, DMSO-d6) δ 11.75 (s, 1H), 10.16 (s, 1H), 10.09 (s, 1H), 8.69 (s, 1H), 8.31 (s, 1H), 8.22 (d, J=8.3 Hz, 1H), 8.15 (s, 1H), 7.94 (d, J=8.2 Hz, 1H), 7.92 (d, J=3.9 Hz, 1H), 7.77 (d, J=7.7 Hz, 1H), 7.64 (d, J=8.8 Hz, 2H), 7.63 (d, J=6.9 Hz, 1H), 7.58 (t, J=8.0 Hz, 1H), 7.44 (d, J=7.7 Hz, 1H), 7.13 (d, J=4.0 Hz, 1H), 6.95 (d, J=9.0 Hz, 2H), 3.74 (t, J=4.6 Hz, 4H), 3.08 (t, J=4.7 Hz, 4H); ESIMS m/z 602.20 (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

Sources & evidence

ORD record
ord-28aa663b6c00458aa13eeef0c22dd5f5
Source dataset
uspto-grants-2008_03
Patent number
US07338957B2

Reaction notes

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