Methanol → HCID 23654007, compound

HRID 597947Notes

Reaction equation

HRID 597947 reaction equation
[CH3:1][CH:2]1[CH2:8][N:7](C(=O)C(F)(F)F)[CH2:6][CH2:5][C:4]2[N:15]=[CH:16][C:17]([NH2:19])=[CH:18][C:3]1=2.C([O-])([O-])=O.[K+].[K+].CO.C([O-])(O)=O.[Na+]>C(Cl)Cl.O>[CH3:1][CH:2]1[CH2:8][NH:7][CH2:6][CH2:5][C:4]2[N:15]=[CH:16][C:17]([NH2:19])=[CH:18][C:3]1=2

Participants

7

Reactant 4

HCID 887MethanolHCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 23654459HCID 23654459, compound

Product 1

HCID 23654007HCID 23654007, compoundYield 24%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-methoxy-5-methyl-3-nitro-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine (2.00 g, 6.00 mmol), HBr/AcOH (33 wt %, 20 ml) and H20 (5 ml) was stirred for 10 min at room temperature. The reaction was parted between sat. aq. NaHCO3 and EtOAc. The organic phased was dried and concentrated in vacuo to give 1.68 g (88%) of pure 5-methyl-3-nitro-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-2-ol. 1H-NMR (CDCl3) δ 8.42 (s, 1H), 4.20-3.20 (m, 8H), 1.45 (d, 1.2H), 1.39 (d, 1.8H) ppm. A mixture of 5-methyl-3-nitro-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-2-ol (1.63 g, 5.10 mmol), Bu4NBr (4.94 g, 15.3 mmol), P2O5 (3.62 g, 12.8 mmol) and toluene (100 ml) was heated to 110° C. for 5 h. The reaction was cooled to room temperature and the liquid part was decanted and concentrated in vacuo to give 1.25 g (64%) of pure 2-bromo-5-methyl-3-nitro-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. 1H-NMR (CDCl3) δ 8.05 (s, 1H), 3.80 (m, 3H), 3.60-3.25 (m, 4H), 1.41 (d, 1.2H), 1.35 (d, 1.8H) ppm. Concurent reduction of the nitro group and halogene on was carried out with 5% Pd/C in MeOH under H2 (1 atm) to give 1.20 g (97%) of pure 5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine. 1H-NMR of rotamers (MeOH-d4) δ 7.77 (2× d, 1H), 7.62 (d, 0.4H), 7.58 (d, 0.6H), 4.10-3.35 (m, 7H), 1.42 (d, 1.3H), 1.35 (d, 1.7H) ppm. A mixture of 5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine (130 mg, 476 μmol), K2CO3 (100 mg), MeOH (6 ml) and H2O (1 ml) was stirred for 16 h at room temprature. The reaction mixture was parted between aq. NaHCO3 and DCM, the organic layer was dried and then concentrated in vacuo. The resulting residue was purified by column chromatography to yield 20.0 mg (24%) of 5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine. 1H-NNMR (MeOH-d4) δ 7.68 (s, 1H), 7.24 (s, 1H), 3.45-2.95 (m, 7H), 1.37 (d, 3H) ppm.

Workup

  1. customthe organic layer was dried
  2. concentrationconcentrated in vacuo
  3. customThe resulting residue was purified by column chromatography

Sources & evidence

ORD record
ord-fe6e192659494c858b83bc3b560b6fc4
Source dataset
uspto-grants-2011_03
Patent number
US07897595B2

Reaction notes

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