Diisopropylethylamine → HCID 178494839, compound

HRID 541321Notes

Reaction equation

HRID 541321 reaction equation
[CH:1]([C:4]1[C:12]([C:13]2[NH:17][C:16]([CH2:18][CH2:19][O:20][CH3:21])=[N:15][N:14]=2)=[CH:11][C:7]([C:8]([OH:10])=O)=[C:6]([CH3:22])[CH:5]=1)([CH3:3])[CH3:2].Cl.[NH:24]1[CH2:29][CH2:28][CH:27]([C:30]2[CH:37]=[CH:36][C:33]([C:34]#[N:35])=[CH:32][CH:31]=2)[CH2:26][CH2:25]1.O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.CCN(C(C)C)C(C)C>C(OCC)(=O)C.CN(C=O)C>[CH:1]([C:4]1[C:12]([C:13]2[NH:17][C:16]([CH2:18][CH2:19][O:20][CH3:21])=[N:15][N:14]=2)=[CH:11][C:7]([C:8]([N:24]2[CH2:29][CH2:28][CH:27]([C:30]3[CH:37]=[CH:36][C:33]([C:34]#[N:35])=[CH:32][CH:31]=3)[CH2:26][CH2:25]2)=[O:10])=[C:6]([CH3:22])[CH:5]=1)([CH3:2])[CH3:3]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 193916184-(Piperidin-4-yl)benzonitrile--hydrogen chloride (1/1)2×HCID 178494842HCID 178494842, compound2×

Product 1

HCID 178494839HCID 178494839, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a 4-mL vial was added 4-Isopropyl-5-(5-(2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-2-methylbenzoic acid (compound 198.6, 31 mg, 0.10 mmol, 1.0 equiv), 4-(piperidin-4-yl)benzonitrile hydrochloride (compound 1.5, 23 mg, 0.10 mmol, 1.0 equiv), 1-hydroxybenzotriazole hydrate (20 wt % water) (22 mg, 0.13 mmol, 1.25 equiv), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (21.5 mg, 0.11 mmol, 1.1 equiv), DMF (1 mL) and DIEA (71 μL, 0.41 mmol, 4 equiv). The mixture was stirred at room temperature for 24 hours then diluted with ethyl acetate (10 mL) and washed with brine (10 mL). The aqueous was back extracted with ethyl acetate (3 mL) and the combined organics was washed with saturated NaHCO3 (5 mL), 1 M NaH2PO4 (5 mL), and brine (5 mL). The organics were dried (Na2SO4), filtered and removed in vacuo. The crude residue was purified by preparative TLC (DCM/8% MeOH) to obtain the title compound as an off white solid (23 mg, 48%). m/z (ES+) 472 (M+H)+.

Workup

  1. washwashed with brine (10 mL)
  2. extractionThe aqueous was back extracted with ethyl acetate (3 mL)
  3. washthe combined organics was washed with saturated NaHCO3 (5 mL), 1 M NaH2PO4 (5 mL), and brine (5 mL)
  4. dry with materialThe organics were dried (Na2SO4)
  5. filtrationfiltered
  6. customremoved in vacuo
  7. customThe crude residue was purified by preparative TLC (DCM/8% MeOH)

Sources & evidence

ORD record
ord-5a2bdc7da98a46f48321d0335fe79844
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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