Hydrochloric Acid → HCID 25153096, compound

HRID 1256659Notes

Reaction equation

HRID 1256659 reaction equation
CC([N:5]([C:9]1[C:10]([NH:21][C:22]([C:24]2[CH:29]=[CH:28][C:27]([CH2:30][NH:31][C:32]([O:34][CH2:35][C:36]3[CH:37]=[N:38][CH:39]=[CH:40][CH:41]=3)=[O:33])=[CH:26][CH:25]=2)=[O:23])=[N:11][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:13][CH:14]=1)C(=O)[O-])(C)C.Cl.O1CCOCC1>C(OCC)(=O)C>[N:38]1[CH:39]=[CH:40][CH:41]=[C:36]([CH2:35][O:34][C:32](=[O:33])[NH:31][CH2:30][C:27]2[CH:26]=[CH:25][C:24]([C:22]([NH:21][C:10]3[C:9]([NH2:5])=[CH:14][CH:13]=[C:12]([C:15]4[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=4)[N:11]=3)=[O:23])=[CH:29][CH:28]=2)[CH:37]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 131730622HCID 131730622, compound

Product 1

HCID 25153096HCID 25153096, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1,1-dimethylethyl{6-phenyl-2-[({4-[({[(pyridin-3-ylmethyl)oxy]carbonyl}amino)methyl]phenyl}carbonyl)amino]pyridin-3-yl}carbamate (25 mg, 0.045 mmol) in ethyl acetate (5 mL) was treated with 4M HCl in dioxane (1.13 mL, 4.52 mmol) and stirred at ambient temperature for 16 hours. The reaction was evaporated in vacuo and purified by flash column chromatography (0-5% methanol(w/1% ammonia)/DCM) to give pyridin-3-ylmethyl[(4-{[(3-amino-6-phenylpyridin-2-yl)amino]carbonyl}phenyl)methyl]carbamate. 1H NMR (CD3OD, 600 MHz) δ 8.58 (br s, 1H), 8.49 (br s, 1H), 8.00 (d, J=8.21 Hz, 2H), 7.89 (d, J=7.63 Hz, 3H), 7.75 (t, J=5.87 Hz, 1H), 7.61 (d, J=8.21 Hz, 1H), 7.58 (d, J=6.75 Hz, 1H), 7.38 (m, 8H), 5.18 (s, 2H), 4.38 (d, J=5.87 Hz, 2H). MS: cal'd 454 (MH+), exp 454 (MH+). The in vitro HDAC1 IC50 of this compound is 84 nM. The IC50 of this compound in HCT-116 cells is 580 nM. Percent Cyp inhibitions at 10 μM are 46, 54 and 55%, for Cyp3A4, 2C9, and 2D6, respectively. The inflection point for MK-499 binding is >30 μM.

Workup

  1. customThe reaction was evaporated in vacuo
  2. custompurified by flash column chromatography (0-5% methanol(w/1% ammonia)/DCM)

Sources & evidence

ORD record
ord-8b712ee45cd9414b9c9a78f0c8e42cb1
Source dataset
uspto-grants-2013_06
Patent number
US08461189B2

Reaction notes

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