1-Hydroxybenzotriazole → US9834551, Example 13

HRID 1500826Notes

Reaction equation

HRID 1500826 reaction equation
[CH3:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([C:11]3[CH:12]=[C:13]([CH:15]=[CH:16][CH:17]=3)[NH2:14])[CH:9]=2)[NH:4][CH:3]=1.[C:18](O)(=[O:23])/[CH:19]=[CH:20]/[CH2:21][CH3:22].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([C:11]3[CH:12]=[C:13]([NH:14][C:18](=[O:23])/[CH:19]=[CH:20]/[CH2:21][CH3:22])[CH:15]=[CH:16][CH:17]=3)[CH:9]=2)[NH:4][CH:3]=1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 638122trans-2-Pentenoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 1176525073-(3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)aniline

Product 1

HCID 86301294US9834551, Example 13Yield 11.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 24 (50 mg, 0.2242 mmol) and trans-2-pentenoic acid 25 (24.6 mg, 0.246 eq) in DMF was added EDC.HCl (33 mg, 0.2706 mmol) and HOBt (36.5 mg, 0.2706 mmol). DIPEA (57.9 mg, 0.448 eq) was added to the reaction, stirred 12 h at RT and check the TLC for completion of the reaction and quench the reaction mixture with dilute water. The organic layer was treated with ethyl acetate (25 mL) and was washed with brine solution (25 mL) and dried over sodium sulphate, filtered and concentrated to get the crude product. The resulting oil was purified through silica gel chromatography using a gradient of 4% Ethyl acetate:hexane to afford 8 mg of Compound 26. MS-ES+305.1 1H NMR (400 MHz, DMSO-D6-d6): 11.45 (s, 1H), 10.08 (s, 1H), 8.40 (s, 1H), 8.17 (s, 1H), 7.85 (d, 1H), 7.61 (m, 1H), 7.36 (m, 2H), 7.30 (d, 1H), 5.62 (m, 1H), 2.35 (s, 3H).

Workup

  1. customfor completion of the reaction
  2. customquench the reaction mixture with dilute water
  3. additionThe organic layer was treated with ethyl acetate (25 mL)
  4. washwas washed with brine solution (25 mL)
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto get the crude product
  9. customThe resulting oil was purified through silica gel chromatography

Sources & evidence

ORD record
ord-3484f4796ae34771a2c955d8b54d2c90
Source dataset
uspto-grants-2015_12
Patent number
US09206188B2

Reaction notes

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