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

HRID 1256672Notes

Reaction equation

HRID 1256672 reaction equation
C(O)(C(F)(F)F)=O.[CH2:8]([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)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>ClCCl>[CH2:8]([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]([NH2:34])=[CH:32][CH:31]=[C:30]([C:42]3[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=3)[N:29]=2)=[O:26])=[CH:21][CH:20]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59627862Benzyl{4-[({3-[(tert-butoxycarbonyl)amino]-6-phenylpyridin-2-yl}amino)carbonyl]benzyl}carbamate

Product 1

HCID 25135288Benzyl(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 of benzyl{4-[({3-[(tert-butoxycarbonyl)amino]-6-phenylpyridin-2-yl}amino)carbonyl]benzyl}carbamate (70 mg, 0.127 mmol) in dichloromethane (1 ml) at room temperature and the reaction was allowed to stir for 1 hour. The reaction was quenched by the addition of saturated sodium bicarbonate until bubbling stopped. The aqueous layer was extracted (2×) with EtOAc. The combined organic fractions were dried over sodium sulfate, filtered and concentrated. The residue was then purified by reverse phase HPLC to provide the desired product. 1H NMR (DMSO-d6) δ: (10.36s, 1H), 7.97 (d, J=8.2 Hz, 2H), 7.90 (d, J=7.3 Hz, 3H), 7.65 (d, J=8.4 Hz, 1H), 7.08-7.41 (m, 1H), 5.12 (s, 2H), 5.02 (s, 2H), 4.26 (d, J=6.3 Hz, 2H) MS: cal'd 453 (MH+), exp 453 (MH+). The in vitro HDAC1 IC50 of this compound is 32 nM. The IC50 of this compound in HCT-116 cells is 590 nM. Percent Cyp inhibitions at 10 μM are 7, 25 and 24%, for Cyp3A4, 2C9, and 2D6, respectively. The inflection point for MK-499 binding is 12.2 μM.

Workup

  1. customThe reaction was quenched by the addition of saturated sodium bicarbonate
  2. customuntil bubbling
  3. extractionThe aqueous layer was extracted (2×) with EtOAc
  4. dry with materialThe combined organic fractions were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was then purified by reverse phase HPLC

Sources & evidence

ORD record
ord-7b19f151412d4f2ebccc3d43cee639bb
Source dataset
uspto-grants-2013_06
Patent number
US08461189B2

Reaction notes

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