Glycolic Acid → (E)-1'-(2-hydroxyacetyl)-6-(3-oxo-3-(4-(thiazol-2-ylmethyl)-5,6-dihydropyridin-1(2H)-yl)prop-1-en-1-yl)-1H-spiro[[1,8]naphthyridine-3,4'-piperidin]-2(4H)-one

HRID 2175755Notes

Reaction equation

HRID 2175755 reaction equation
CCN(C(C)C)C(C)C.FC(F)(F)C(O)=O.[O:17]=[C:18]([N:37]1[CH2:42][CH2:41][C:40]([CH2:43][C:44]2[S:45][CH:46]=[CH:47][N:48]=2)=[CH:39][CH2:38]1)/[CH:19]=[CH:20]/[C:21]1[CH:22]=[C:23]2[C:33](=[N:34][CH:35]=1)[NH:32][C:31](=[O:36])[C:25]1([CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1)[CH2:24]2.[C:49](O)(=[O:52])[CH2:50][OH:51].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>CN(C=O)C.O>[OH:52][CH2:49][C:50]([N:28]1[CH2:29][CH2:30][C:25]2([CH2:24][C:23]3[C:33](=[N:34][CH:35]=[C:21](/[CH:20]=[CH:19]/[C:18](=[O:17])[N:37]4[CH2:42][CH2:41][C:40]([CH2:43][C:44]5[S:45][CH:46]=[CH:47][N:48]=5)=[CH:39][CH2:38]4)[CH:22]=3)[NH:32][C:31]2=[O:36])[CH2:26][CH2:27]1)=[O:51]

Participants

8

Reactant 5

HCID 757Glycolic AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86297851(E)-6-(3-oxo-3-(4-(thiazol-2-ylmethyl)-5,6-dihydropyridin-1(2H)-yl)prop-1-en-1-yl)-1H-spiro[[1,8]naph-thyridine-3,4'-piperidin]-2(4H)-one 2,2,2-trifluoroacetate2×

Product 1

HCID 86297854(E)-1'-(2-hydroxyacetyl)-6-(3-oxo-3-(4-(thiazol-2-ylmethyl)-5,6-dihydropyridin-1(2H)-yl)prop-1-en-1-yl)-1H-spiro[[1,8]naphthyridine-3,4'-piperidin]-2(4H)-oneYield 22.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
27.5 °C

Procedure

DIPEA (0.38 mL, 2.13 mmol) was added to a stirred solution of (E)-6-(3-oxo-3-(4-(thiazol-2-ylmethyl)-5,6-dihydropyridin-1(2H)-yl)prop-1-en-1-yl)-1H-spiro[[1,8]naph-thyridine-3,4′-piperidin]-2(4H)-one 2,2,2-trifluoroacetate (Compound 34) (200 mg, 0.35 mmol), Glycolic acid (80 mg, 1.06 mmol), HOBt (96 mg, 0.70 mmol) and EDC.HCl (170 mg, 0.88 mmol) in dry DMF (4 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 diluted with water (30 mL) and extracted with ethyl acetate (2×30 mL). The organic layer was washed with brine (30 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 a light yellow solid (40 mg, 22%); 1H NMR (400 MHz, DMSO-d6) δ 10.75 (s, 1H), 8.38 (d, J=2.0 Hz, 1H), 8.09 (s, 1H), 7.71 (d, J=3.4 Hz, 1H), 7.61 (d, J=3.5 Hz, 1H), 7.45 (d, J=15.7 Hz, 1H), 7.28-7.14 (m, 1H), 5.68-5.66 (m, 1H), 4.50 (t, J=5.4 Hz, 1H), 4.28-4.22 (m, 1H), 4.10-4.04 (m, 3H), 3.78-3.74 (m, 3H), 3.74-3.62 (m, 3H), 3.54-3.38 (m, 2H), 2.96 (s, 2H), 2.20-2.06 (m, 2H), 1.86-1.68 (m, 2H), 0.46-0.32 (m, 2H); ES-MS: 508.2 (M+1)+.

Workup

  1. extractionextracted with ethyl acetate (2×30 mL)
  2. washThe organic layer was washed with brine (30 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-0dd8405b2c0d4861a497985bb66226cd
Source dataset
uspto-grants-2015_06
Patent number
US09062075B2

Reaction notes

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