7-[(6-ethyl-2-phenyl-piperidin-3-ylamino)-methyl]-6-methoxy-1-methyl-3,4-dihydro-1H-[1,5]naphthyridin-2-one → 6-methoxy-1-methyl-7-[(2(S)-phenyl-6(S)-propyl-piperidin-3(S)-ylamino)-methyl]-3,4-dihydro-1H-[1,5]naphthyridin-2-one

HRID 1244061Notes

Reaction equation

HRID 1244061 reaction equation
[CH3:1]OC1C(C=O)=CC2N(C)C(=O)CCC=2N=1.[CH2:17]([CH:19]1[NH:24][CH:23]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:22]([NH:31][CH2:32][C:33]2[CH:42]=[C:41]3[C:36]([CH2:37][CH2:38][C:39](=[O:44])[N:40]3[CH3:43])=[N:35][C:34]=2[O:45][CH3:46])[CH2:21][CH2:20]1)[CH3:18]>CCCCCCC.C(O)C>[CH3:46][O:45][C:34]1[N:35]=[C:36]2[C:41](=[CH:42][C:33]=1[CH2:32][NH:31][C@H:22]1[CH2:21][CH2:20][C@H:19]([CH2:17][CH2:18][CH3:1])[NH:24][C@H:23]1[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)[N:40]([CH3:43])[C:39](=[O:44])[CH2:38][CH2:37]2

Participants

4

Reactant 2

HCID 219317147-[(6-ethyl-2-phenyl-piperidin-3-ylamino)-methyl]-6-methoxy-1-methyl-3,4-dihydro-1H-[1,5]naphthyridin-2-oneHCID 219317642-Methoxy-5-methyl-6-oxo-5,6,7,8-tetrahydro-[1,5]naphthyridine-3-carbaldehyde

Product 1

HCID 210693286-methoxy-1-methyl-7-[(2(S)-phenyl-6(S)-propyl-piperidin-3(S)-ylamino)-methyl]-3,4-dihydro-1H-[1,5]naphthyridin-2-one

Reagents, catalysts & solvents 1

HCID 22502148Ethanol heptaneSolvent

Procedure

By a procedure similar to the previous example 74: starting with cis-2-phenyl-3-amino-trans-6-(n-propyl)-piperidine (Scheme J) and 2-methoxy-5-methyl-6-oxo-5,6,7,8-tetrahydro-[1,5]naphthyridine-3-carbaldehyde (Example 74, step 5) and using the above coupling procedure (Example 74, step 6) 7-[(6-ethyl-2-phenyl-piperidin-3-ylamino)-methyl]-6-methoxy-1-methyl-3,4-dihydro-1H-[1,5]naphthyridin-2-one was obtained. Using a CHIRALPAK AD (10×50 cm) and a mobil phase of 95:5 heptane/ethanol containing 0.025% diethyl amine (flow rate=275 ml/min) 6-methoxy-1-methyl-7-[(2(S)-phenyl-6(S)-propyl-piperidin-3(S)-ylamino)-methyl]-3,4-dihydro-1H-[1,5]naphthyridin-2-one (retention time 11.479 min) was isolated as a pure enantiomer. 1H NMR (CDCl3) δ 7.40 (m, 2H), 7.30 (m, 2H), 7.22 (m, 1H), 6.95 (s, 1H), 4.20 (s, 1H), 3.72 (s, 3H), 3.80, 3.62 (d,d, 2H), 3.20 (m, 1H), 3.10 (s, 3H), 2.90 (m, 2H), 2.85 (m, 1H), 2.62 (m, 2H), 2.10 (m, 2H), 1.90 (m, 3H), 1.70 (m, 1H), 1.42 (m, 1H), 1.30 (m, 3H), 0.9 (t, 3H). Mass spectrum: m/e=423.2 (p+1). The corresponding enantiomer 6-methoxy-1-methyl-7-[(2(R)-phenyl-6(R)-propyl-piperidin-3(R)-ylamino)-methyl]-3,4-dihydro-1H-[1,5]naphthyridin-2-one (retention time 11.592 min) was also isolated. NMR and mass spectrum was identical to the above spectra.

Workup

  1. customwas obtained

Sources & evidence

ORD record
ord-2180b3264e8149f49d6dca75c8ce7162
Source dataset
uspto-grants-2006_10
Patent number
US07119207B2

Reaction notes

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