Trifluoroacetic acid → Pyridin-2-ylmethyl(4-{[(3-amino-6-phenylpyridin-2-yl)amino]carbonyl}benzyl)carbamate

HRID 1256674Notes

Reaction equation

HRID 1256674 reaction equation
C(O)(C(F)(F)F)=O.[N:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:14][O:15][C:16](=[O:48])[NH:17][CH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]([NH:27][C:28]2[C:33]([NH:34]C(OC(C)(C)C)=O)=[CH:32][CH:31]=[C:30]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[N:29]=2)=[O:26])=[CH:21][CH:20]=1>ClCCl>[N:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:14][O:15][C:16](=[O:48])[NH:17][CH2:18][C:19]1[CH:20]=[CH:21][C:22]([C:25]([NH:27][C:28]2[C:33]([NH2:34])=[CH:32][CH:31]=[C:30]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[N:29]=2)=[O:26])=[CH:23][CH:24]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59627872Pyridin-2-ylmethyl{4-[({3-[(tert-butoxycarbonyl)amino]-6-phenylpyridin-2-yl}amino)carbonyl]benzyl}carbamate

Product 1

HCID 25153921Pyridin-2-ylmethyl(4-{[(3-amino-6-phenylpyridin-2-yl)amino]carbonyl}benzyl)carbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (1 mL, 12.98 mmol) was added to a flask containing pyridin-2-ylmethyl{4-[({3-[(tert-butoxycarbonyl)amino]-6-phenylpyridin-2-yl}amino)carbonyl]benzyl}carbamate (100 mg, 0.181 mmol) in dichloromethane (2 ml) and the mixture stirred at room temperature for 1 hour. The reaction was quenched by the addition of saturated sodium bicarbonate until bubbling stopped. The aqueous layer was extracted (3×) with EtOAc and dried over sodium sulfate. The organic product was purified using HPLC. LCMS of the major UV absorbant fraction indicated the presence of the desired product. 1H NMR (DMSO-d6) δ: 10.36 (s, 1H), 8.51 (d, J=4 Hz, 1H), 7.96-8.05 (m, 3H), 7.88-7.94 (m, 2H), 7.76-7.82 (m, 1H), 7.65 (d, J=8.3 Hz 1H), 7.32-7.45 (m, 5H), 7.18-7.32 (m, 3H), 5.12 (s, 2H), 5.09 (s, 2H), 4.28 (d, J=6.2 Hz, 2H) MS: cal'd 454 (MH+), exp 454 (MH+). The in vitro HDAC1 IC50 of this compound is 35 nM. The IC50 of this compound in HCT-116 cells is 560 nM. Percent Cyp inhibitions at 10 μM are 27, 47 and 24%, for Cyp3A4, 2C9, and 2D6, respectively. The inflection point for MK-499 binding is 2535 μM.

Workup

  1. customThe reaction was quenched by the addition of saturated sodium bicarbonate
  2. customuntil bubbling
  3. extractionThe aqueous layer was extracted (3×) with EtOAc
  4. dry with materialdried over sodium sulfate
  5. customThe organic product was purified

Sources & evidence

ORD record
ord-b0814762a75745dfa4dcdfe7ecd9cd61
Source dataset
uspto-grants-2013_06
Patent number
US08461189B2

Reaction notes

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