1-Hydroxybenzotriazole → (E)-3,3-dimethyl-6-(3-oxo-3-(4-(thiazol-2-ylmethyl)-5,6-dihydropyridin-1(2H)-yl)prop-1-en-1-yl)-3,4-dihydro-1,8-naphthyridin-2(1H)-one

HRID 2175752Notes

Reaction equation

HRID 2175752 reaction equation
CCN(C(C)C)C(C)C.Cl.[NH:11]1[CH2:16][CH:15]=[C:14]([CH2:17][C:18]2[S:19][CH:20]=[CH:21][N:22]=2)[CH2:13][CH2:12]1.[CH3:23][C:24]1([CH3:40])[C:33](=[O:34])[NH:32][C:31]2[N:30]=[CH:29][C:28](/[CH:35]=[CH:36]/[C:37](O)=[O:38])=[CH:27][C:26]=2[CH2:25]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>CN(C=O)C>[CH3:23][C:24]1([CH3:40])[CH2:25][C:26]2[C:31](=[N:30][CH:29]=[C:28](/[CH:35]=[CH:36]/[C:37](=[O:38])[N:11]3[CH2:12][CH2:13][C:14]([CH2:17][C:18]4[S:19][CH:20]=[CH:21][N:22]=4)=[CH:15][CH2:16]3)[CH:27]=2)[NH:32][C:33]1=[O:34]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 59277535(E)-3-(6,6-dimethyl-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylic acidHCID 904115082-((1,2,3,6-Tetrahydropyridin-4-yl)methyl)thiazole hydrochloride

Product 1

HCID 86297446(E)-3,3-dimethyl-6-(3-oxo-3-(4-(thiazol-2-ylmethyl)-5,6-dihydropyridin-1(2H)-yl)prop-1-en-1-yl)-3,4-dihydro-1,8-naphthyridin-2(1H)-oneYield 64.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
27.5 °C

Procedure

DIPEA (0.33 mL, 1.83 mmol) was added to a stirred solution of 2-((1,2,3,6-tetrahydro-pyridin-4-yl)methyl)thiazole hydrochloride (Intermediate-2) (158 mg, 0.73 mmol), (E)-3-(6,6-dimethyl-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylic acid (Intermediate-22) (150 mg, 0.61 mmol), HOBt (98 mg, 0.73 mmol) and EDC.HCl (232 mg, 1.22 mmol) in dry DMF (2 mL) at 20-35° C. and the reaction mixture was allowed to stir at 20-35° C. for 16 h. Then the reaction mixture was poured into ice water (50 mL) and extracted with ethyl acetate (2×50 mL). The organic layer was washed with brine (50 mL), dried over anhydrous Na2SO4 and filtered. The filtrate was rotary evaporated under vacuum to get residue which was purified by column chromatography using mixture of 4% methanol/dichloromethane as an eluent to get the desired compound as an off-white solid (160 mg, 51%); 1H NMR (400 MHz, DMSO-d6) δ 10.61 (s, 1H), 8.36 (s, 1H), 8.08 (s, 1H), 7.71 (d, J=2.9 Hz, 1H), 7.61 (d, J=3.0 Hz, 1H), 7.45 (d, J=15.2 Hz, 1H), 7.30-7.14 (m, 1H), 5.68-5.65 (m, 1H), 4.28-4.20 (m, 1H), 4.08-4.02 (m, 1H), 3.80-3.72 (m, 3H), 3.68-3.60 (m, 1H), 2.79 (s, 2H), 2.18-2.04 (m, 2H), 1.08 (s, 6H); LC-MS: 409.2 (M+1)+.

Workup

  1. extractionextracted with ethyl acetate (2×50 mL)
  2. washThe organic layer was washed with brine (50 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. customThe filtrate was rotary evaporated under vacuum
  6. customto get residue which
  7. customwas purified by column chromatography
  8. additionmixture of 4% methanol/dichloromethane as an eluent

Sources & evidence

ORD record
ord-3cb318ddd9344a949dc9ad3df67cb4aa
Source dataset
uspto-grants-2015_06
Patent number
US09062075B2

Reaction notes

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