Hydrochloric Acid → HCID 67372434, compound

HRID 1971976Notes

Reaction equation

HRID 1971976 reaction equation
[CH2:1]([C:5]1[N:6]=[N:7][C:8]([O:28][CH:29]2[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]2)=[CH:9][C:10]=1[C:11]1[CH:27]=[CH:26][C:14]([O:15][CH2:16][CH:17]2[CH2:22][CH2:21][CH:20]([C:23](O)=[O:24])[CH2:19][CH2:18]2)=[CH:13][CH:12]=1)[CH2:2][CH2:3][CH3:4].[ClH:36].[CH3:37][NH:38][CH3:39].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl>CN(C=O)C.O.CCOC(C)=O.C(O)(=O)C.C(Cl)Cl.CCOCC>[ClH:36].[ClH:36].[CH3:37][N:38]([CH3:39])[C:23]([CH:20]1[CH2:21][CH2:22][CH:17]([CH2:16][O:15][C:14]2[CH:13]=[CH:12][C:11]([C:10]3[CH:9]=[C:8]([O:28][CH:29]4[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]4)[N:7]=[N:6][C:5]=3[CH2:1][CH2:2][CH2:3][CH3:4])=[CH:27][CH:26]=2)[CH2:18][CH2:19]1)=[O:24]

Participants

11

Reactant 5

HCID 313Hydrochloric AcidHCID 10473Dimethylamine, hydrochlorideHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67373540HCID 67373540, compound

Product 1

HCID 67372434HCID 67372434, compoundYield 102%

Reagents, catalysts & solvents 5

HCID 176Acetic AcidSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 22728543Water ethylacetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 4-{4-[3-butyl-6-(1-methyl-piperidin-4-yloxy)-pyridazin-4-yl]-phenoxymethyl}-cyclohexanecarboxylic acid (0.2 mmol, 97 mg) in DMF (1 mL) was added dimethylamine hydrochloride (0.3 mmol, 25 mg), HBTU (0.4 mmol, 152 mg), DIEA (0.4 mmol, 70 μL). The mixture was stirred at 100° C. for 2 hours. The mixture was then diluted with water/EtOAc and neutralized with acetic acid. The organic layers were combined, dried, and condensed in vacuo and the residue was purified by silica gel chromatography (DCM to DCM+10% in MeOH) to give a colorless sticky solid, which was dissolved in DCM (1 mL), 2N HCl in ether (1 mL) was added, kept at room temperature for 10 min, condensed, triturated with hexanes to provide the title compound (89 mg). LCMS: m/z 510 [M+1]. 1H NMR (400 MHz, CD3OD): δ 7.64 and 7.76 (1H, s), 7.45-7.51 (2H, m), 7.13-7.17 (2H, m), 5.37-5.54 (1H, m), 4.30 (2H, d), 3.35-3.69 (3H, m), 3.08-3.30 (4H, m), 2.94 (3H, s), 2.81 (6H, s), 2.21-2.74 (5H, m), 1.86-2.98 (2H, m), 1.25-1.54 (10H, m), 0.82 (3H, t).

Workup

  1. customdried
  2. customcondensed in vacuo
  3. customthe residue was purified by silica gel chromatography (DCM to DCM+10% in MeOH)
  4. customto give a colorless sticky solid, which
  5. waitkept at room temperature for 10 min
  6. customcondensed
  7. customtriturated with hexanes

Sources & evidence

ORD record
ord-ab2fdd0566b24b9285047ed9c3c87b46
Source dataset
uspto-grants-2013_04
Patent number
US08431575B2

Reaction notes

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