Hydrochloric Acid → 3-Trifluoromethyl-pyrazine-2-carboxylic acid (9-isopropyl-1,2,3,4-tetrahydro-1,4-methano-naphthalen-5-yl)-amide

HRID 535786Notes

Reaction equation

HRID 535786 reaction equation
[CH:1]([CH:4]1[CH:8]2[C:9]3[C:14]([CH:5]1[CH2:6][CH2:7]2)=[CH:13][CH:12]=[CH:11][C:10]=3[NH2:15])([CH3:3])[CH3:2].C[Al](C)C.[F:20][C:21]([F:33])([F:32])[C:22]1[C:23]([C:28](OC)=[O:29])=[N:24][CH:25]=[CH:26][N:27]=1.Cl>ClCCl>[CH:1]([CH:4]1[CH:8]2[C:9]3[C:14]([CH:5]1[CH2:6][CH2:7]2)=[CH:13][CH:12]=[CH:11][C:10]=3[NH:15][C:28]([C:23]1[C:22]([C:21]([F:32])([F:20])[F:33])=[N:27][CH:26]=[CH:25][N:24]=1)=[O:29])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 16682925TrimethylaluminumHCID 58542464Methyl 3-(trifluoromethyl)pyrazine-2-carboxylateHCID 594313419-Isopropyl-1,2,3,4-tetrahydro-1,4-methanonaphthalen-5-amine

Product 1

HCID 585424623-Trifluoromethyl-pyrazine-2-carboxylic acid (9-isopropyl-1,2,3,4-tetrahydro-1,4-methano-naphthalen-5-yl)-amideYield 80.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a 1-ml vial containing 9-isopropyl-1,2,3,4-tetrahydro-1,4-methano-naphthalen-5-ylamine (6) (0.1 g, 0.497 mmol) and DCM (Volume: 2 mL) was added a 2.0 M solution of trimethylaluminum (0.017 g, 0.243 mmol). After evolution of gas ceased, methyl 3-(trifluoromethyl)pyrazine-2-carboxylate (8) (0.113 g, 0.546 mmol) was added as a solution in dichloromethane (0.5 ml) and the mixture was stirred at room temperature overnight. The reaction mixture was poured into 2N HCl (5 ml) and after bubbling ceased, was extracted with dichloromethane (2×5 ml) and was passed through a Biotage phase separator. The organic extracts were combined and the solvent was removed. The residue was loaded onto a silica column and was eluted using a ethyl acetate/hexanes gradient to afford the title compound (0.15 g, 80%) as a white solid with 4:1 syn:anti product: mp 173-177° C.; 1H NMR (600 MHz, CDCl3) δ 9.33 (s, 1H), 8.90 (d, J=2.2 Hz, 1H), 8.86 (d, J=2.3 Hz, 1H), 7.97 (d, J=8.4 Hz, 1H), 7.20-7.14 (m, 1H), 7.06 (d, J=7.2 Hz, 1H), 3.40 (s, 1H), 3.28 (s, 1H), 2.02-2.00 (m, 2H), 1.65 (d, J=10.0 Hz, 1H), 1.32-1.18 (m, 2H), 1.05-0.98 (m, 1H), 0.84 (d, J=6.6 Hz, 6H); ESIMS m/z 376.3 ([M+H]+), m/z 374.4 ([M−H])−).

Workup

  1. customafter bubbling
  2. extractionwas extracted with dichloromethane (2×5 ml)
  3. customthe solvent was removed
  4. washwas eluted

Sources & evidence

ORD record
ord-59133f99129d46c79fdf8da73fdc626d
Source dataset
uspto-grants-2014_10
Patent number
US08859558B2

Reaction notes

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