1-Hydroxybenzotriazole → HCID 86732062, compound

HRID 1498798Notes

Reaction equation

HRID 1498798 reaction equation
[CH3:1][C:2]1[N:6]=[C:5]([CH3:7])[N:4]([C:8]2[CH:13]=[C:12]([C@@H:14]3[CH2:16][C@H:15]3[C:17](O)=O)[CH:11]=[C:10]([CH3:20])[N:9]=2)[N:3]=1.[CH3:21][NH:22][C:23]1[C:24]([NH2:29])=[CH:25][CH:26]=[CH:27][CH:28]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>O1CCCC1>[CH3:1][C:2]1[N:6]=[C:5]([CH3:7])[N:4]([C:8]2[CH:13]=[C:12]([C@@H:14]3[CH2:16][C@H:15]3[C:17]3[N:22]([CH3:21])[C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[N:29]=3)[CH:11]=[C:10]([CH3:20])[N:9]=2)[N:3]=1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 78498N-Methyl-o-phenylenediamineHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86732061HCID 86732061, compound

Product 1

HCID 86732062HCID 86732062, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of trans-2-(2-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-6-methylpyridin-4-yl)cyclopropanecarboxylic acid (25-3) (45 mg, 0.165 mmol), N1-methylbenzene-1,2-diamine (28 mg, 0.231 mmol), EDC.HCl (47 mg, 0.248 mmol), HOBt (38 mg, 0.248 mmol), diisopropylethylamine (85 mg, 0.660 mmol), and tetrahydrofuran (3 mL) was stirred at room temperature overnight and evaporated. Acetic acid (3 mL) was added and the mixture was heated at 95° C. for 1 hour, cooled to room temperature, and evaporated. The residue was partitioned between ethyl acetate and saturated aqueous NaHCO3 solution. The extract was washed with brine, dried over sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography (5-10% methanol in DCM) and reverse phase (10-100% acetonitrile in water) to give trans-2-(2-(2-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-6-methylpyridin-4-yl)cyclopropyl)-1-methyl-1H-benzo[d]imidazole (25-4) as an off-white solid. 1H NMR (300 MHz, CDCl3) δ 7.74-7.65 (m, 1H), 7.38 (br s, 1H), 7.34-7.20 (m, 3H), 6.98 (br s, 1H), 3.81 (s, 3H), 2.83 (s, 3H), 2.78-2.67 (m, 1H), 2.54 (s, 3H), 2.46-2.36 (m, 1H), 2.41 (s, 3H), 2.12-2.02 (m, 1H), 1.80-1.69 (m, 1H). LRMS m/z (M+H) 359 found, 359 required. m.p. 157-159° C.

Workup

  1. customevaporated
  2. additionAcetic acid (3 mL) was added
  3. temperaturethe mixture was heated at 95° C. for 1 hour
  4. temperaturecooled to room temperature
  5. customevaporated
  6. customThe residue was partitioned between ethyl acetate and saturated aqueous NaHCO3 solution
  7. washThe extract was washed with brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. customThe residue was purified by silica gel column chromatography (5-10% methanol in DCM) and reverse phase (10-100% acetonitrile in water)

Sources & evidence

ORD record
ord-5058ca4ef3a442d990507e045ceacc48
Source dataset
uspto-grants-2015_12
Patent number
US09200001B2

Reaction notes

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