Trifluoroacetic acid → HCID 178424542, compound

HRID 1711321Notes

Reaction equation

HRID 1711321 reaction equation
[C:1]([C:3]1[N:4]=[C:5]([C:8]([NH:10][C:11]2[CH:19]=[CH:18][C:14]([C:15](O)=[O:16])=[CH:13][C:12]=2[C:20]2[CH2:25][CH2:24][C:23]([CH3:27])([CH3:26])[CH2:22][CH:21]=2)=[O:9])[NH:6][CH:7]=1)#[N:2].Cl.C([O:31][C:32](=[O:42])[C@H:33]([CH2:35][CH2:36][C:37]([O:39]CC)=[O:38])[NH2:34])C.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C.[OH-].[K+].C(O)(C(F)(F)F)=O>CCOC(C)=O.C(Cl)Cl>[C:1]([C:3]1[N:4]=[C:5]([C:8]([NH:10][C:11]2[CH:19]=[CH:18][C:14]([C:15]([NH:34][C@H:33]([C:32]([OH:31])=[O:42])[CH2:35][CH2:36][C:37]([OH:39])=[O:38])=[O:16])=[CH:13][C:12]=2[C:20]2[CH2:25][CH2:24][C:23]([CH3:27])([CH3:26])[CH2:22][CH:21]=2)=[O:9])[NH:6][CH:7]=1)#[N:2]

Participants

10

Reactant 7

HCID 6422Trifluoroacetic acidHCID 14797Potassium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 73960Glutamic acid diethyl ester hydrochlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 178424543HCID 178424543, compound

Product 1

HCID 178424542HCID 178424542, compoundYield 52%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A flask was charged with 4-[(4-cyano-1H-imidazole-2-carbonyl)-amino]-3-(4,4-dimethyl-cyclohex-1-enyl)-benzoic acid (36 mg, 99 μmol)(prepared in Example 65), L-glutamic acid diethyl ester hydrochloride (26 mg, 120 μmol), N-(3-dimethylamino-propyl)-N′-ethylcarbodiimide (23 mg, 120 μmol), 1-hydroxybenzotriazole (13 mg, 99 μmol), DIEA (38 mg, 300 μmol) and 0.3 mL of DCM and stirred for 8 h at RT. The mixture was diluted with 20 mL EtOAc, washed with NaHCO3 (2×20 mL) and brine (20 mL), and the organic layer was dried (Na2SO4) and concentrated. The residue was dissolved in 2 mL of EtOH and a 7 N aqueous KOH solution (43 μL, 300 μmol) was added and the reaction stirred for 8 h at RT. The pH was adjusted to 2 with a 2 N TFA solution and the title compound was purified by RP-HPLC eluting with a linear gradient of 30% to 50% acetonitrile in 0.1% TFA/H2O over 10 min on a C18 column giving 25 mg (52%) of a white solid. 1H-NMR (CD3OD, 400 MHz): δ 8.35 (d, J=8.6 Hz, 1H), 7.92 (s, 1H), 7.72 (dd, J=8.6, 2.1 Hz, 1H), 7.66 (d, J=2.1 Hz, 1H), 5.74 (m, 1H), 4.54 (m, 1H), 2.39 (t, J=7.4 Hz, 2H), 2.30-2.16 (m, 3H), 2.07-1.95 (m, 3H), 1.54 (t, J=6.3 Hz, 2H), 1.03 (s, 6H). Mass spectrum (ESI, m/z): Calcd. for C25H27N5O6, 494.2 (M+H), found 494.1.

Workup

  1. washwashed with NaHCO3 (2×20 mL) and brine (20 mL)
  2. dry with materialthe organic layer was dried (Na2SO4)
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in 2 mL of EtOH
  5. stirringthe reaction stirred for 8 h at RT
  6. customthe title compound was purified by RP-HPLC
  7. washeluting with a linear gradient of 30% to 50% acetonitrile in 0.1% TFA/H2O over 10 min on a C18 column

Sources & evidence

ORD record
ord-bb246c05682849aa9a11b59794a5af35
Source dataset
uspto-grants-2010_09
Patent number
US07790724B2

Reaction notes

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