5-Methyl-1H-imidazole-4-carbaldehyde → HCID 178486435, compound

HRID 1244004Notes

Reaction equation

HRID 1244004 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[CH2:13][NH:14][C@H:15]1[CH2:20][CH2:19][CH2:18][NH:17][C@H:16]1[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[N:9]([CH3:27])[C:8](=[O:28])[CH2:7][CH2:6]2.[CH3:29][C:30]1[N:31]=[CH:32][NH:33][C:34]=1[CH:35]=O.C([BH3-])#N.[Na+]>C(O)(=O)C.CO.C1COCC1.C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[CH2:13][NH:14][C@H:15]1[CH2:20][CH2:19][CH2:18][N:17]([CH2:29][C:30]3[NH:31][CH:32]=[N:33][C:34]=3[CH3:35])[C@H:16]1[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[N:9]([CH3:27])[C:8](=[O:28])[CH2:7][CH2:6]2

Participants

8

Reactant 3

HCID 27958875-Methyl-1H-imidazole-4-carbaldehydeHCID 5003444Sodium cyanoborohydrideHCID 103093706-Methoxy-1-methyl-7-[(2S,3S)-(2-phenyl-piperidin-3-ylamino)-methyl]-3,4-dihydro-1H-quinolin-2-one

Product 1

HCID 178486435HCID 178486435, compoundYield 67.4%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To 6-Methoxy-1-methyl-7-[(2S,3S)-(2-phenyl-piperidin-3-ylamino)-methyl]-3,4-dihydro-1H-quinolin-2-one (100 mg, 0.26 mmol), 4-methyl-5-imidazolecarboxaldehyde (116 mg, 1.06 mmol), and 5 drops acetic acid in 2 mL of methanol at room temperature was added 1.58 mL (1.58 mmol) of 1.0 M sodium cyanoborohydride in THF. The resultant mixture was stirred for 1 hour at room temperature and then at 50° C. for 3 days. The reaction was then diluted with methylene chloride and washed 1× with sat'd. NaHCO3, dried over MgSO4, filtered, and concentrated. Silica gel chroatography (9:1 ethyl acetate/methanol) gave 83 mg (66%) of the title compound, a white foam. Rf=0.05 (9:1 ethyl acetate/methanol). MS (M+H)+=474.2; 1H NMR (400 MHz, CDCl3): δ 1.35–1.45 (m, 2H), 1.85–1.95 (bd, 1H), 1.99 (s, 3H), 1.99–2.15 (m, 2H), 2.45–2.55 (t, J=7.4 Hz, 2H), 2.62–2.65 (bs, 1H), 2.70–2.80 (t, J=7.4 Hz, 2H), 2.90–2.95 (d, J=13.9 Hz, 1H), 3.00–3.05 (d, J=10.7 Hz, 1H), 3.10 (s, 3H), 3.35–3.40 (m, 2H), 3.47 (s, 3H), 3.60–3.65 (d, J=14.3 Hz, 2H), 6.46 (s, 1H), 6.60 (s, 1H), 7.15–7.30 (m, 3H), 7.35–7.45 (m, 2H); 13C NMR (100 MHz, CDCl3): δ 11.4, 20.1, 25.5, 27.4, 29.6, 31.8, 45.3, 50.3, 53.7, 55.5, 56.2, 71.8, 109.8, 116.1, 125.2, 127.1, 128.2, 128.8, 133.2, 133.4, 141.2, 152.9, 170.0. The dihydrochloride salt was prepared by the addition of 2 M HCl in ether to a solution of the product in ethyl acetate. Concentration gave a white solid (Mp=225–229° C.).

Workup

  1. washwashed 1× with sat'd
  2. dry with materialNaHCO3, dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-eafd5e00c5f64d6098b786506833d83c
Source dataset
uspto-grants-2006_10
Patent number
US07119207B2

Reaction notes

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