4-Formylbenzoic acid → HCID 178524380, compound

HRID 529327Notes

Reaction equation

HRID 529327 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([CH2:8][N:9]([C@@H:16]2[CH2:18][C@H:17]2[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)C(=O)C(F)(F)F)[CH2:4][CH2:3]1.[CH:25]([C:27]1[CH:35]=[CH:34][C:30]([C:31]([OH:33])=[O:32])=[CH:29][CH:28]=1)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[C:19]1([C@@H:17]2[CH2:18][C@H:16]2[NH:9][CH2:8][C@H:5]2[CH2:4][CH2:3][C@H:2]([NH:1][CH2:25][C:27]3[CH:35]=[CH:34][C:30]([C:31]([OH:33])=[O:32])=[CH:29][CH:28]=3)[CH2:7][CH2:6]2)[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

5

Reactant 3

HCID 120884-Formylbenzoic acidHCID 5049666Sodium triacetoxyborohydrideHCID 178511554HCID 178511554, compound

Product 1

HCID 178524380HCID 178524380, compoundYield 51.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of N-((trans-4-aminocyclohexyl)methyl)-2,2,2-trifluoro-N-(trans-2-phenylcyclopropyl)acetamide (100 mg, 0.294 mmol) in 1,2-dichloroethane (3 mL) was added 4-formylbenzoic acid (48.5 mg, 0.323 mmol). The reaction mixture was refluxed for 2 minutes, then cooled down to room temperature. Sodium triacetoxyborohydride (187 mg, 0.881 mmol) was added. The reaction mixture was stirred 1 hour at room temperature. The reaction mixture was evaporated, and dissolved in 1 mL of water and 2 mL of methanol. The reaction mixture was injected on preparatory HPLC (5 to 40% AcCN: H2O with 0.1% formic acid modifier). The fractions were collected and evaporated. The resulting oil was dissolved in 6 ml of EtOH and 3 ml of 1 M NaOH. The reaction mixture was stirred for 20 minutes then it was evaporated. The resulting product was injected on preparatory HPLC (2 to 20% AcCN: H2O with 0.1% formic acid modifier). The fractions were collected and evaporated. 1 mL of 1 M HCl was added to each fraction and product was evaporated. 4-(((trans-4-(((trans-2-Phenylcyclopropyl)amino)methyl)cyclohexyl)amino)methyl)benzoic acid (60 mg, 0.151 mmol, 51.3% yield) was isolated as white solid. 1H NMR (400 MHz, DMSO-d6) δ 12.68-13.69 (m, 1H), 9.23-9.66 (m, 4H), 7.99 (d, J=8.34 Hz, 2H), 7.72 (d, J=8.34 Hz, 2H), 7.28-7.35 (m, 2H), 7.11-7.26 (m, 3H), 4.24 (br. s., 2H), 2.79-3.09 (m, 4H), 2.58 (ddd, J=3.54, 6.38, 10.04 Hz, 1H), 2.20 (d, J=10.36 Hz, 2H), 1.96 (d, J=11.12 Hz, 2H), 1.65-1.85 (m, 1H), 1.54-1.66 (m, 1H), 1.46 (q, J=12.38 Hz, 2H), 1.18-1.34 (m, 1H), 1.03 (q, J=12.04 Hz, 2H); LC-MS Rt=0.56 min; MS (ESI): 379.4 [M+H]+.

Workup

  1. temperatureThe reaction mixture was refluxed for 2 minutes
  2. customThe reaction mixture was evaporated
  3. dissolutiondissolved in 1 mL of water
  4. customThe fractions were collected
  5. customevaporated
  6. dissolutionThe resulting oil was dissolved in 6 ml of EtOH
  7. stirringThe reaction mixture was stirred for 20 minutes
  8. customit was evaporated
  9. customThe fractions were collected
  10. customevaporated
  11. addition1 mL of 1 M HCl was added to each fraction and product
  12. customwas evaporated

Sources & evidence

ORD record
ord-616cdb3807aa4a68a6fa42759a7611a0
Source dataset
uspto-grants-2016_05
Patent number
US09346840B2

Reaction notes

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