Formaldehyde → (E)-1'-methyl-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 2175754Notes

Reaction equation

HRID 2175754 reaction equation
F[C:2](F)(F)C(O)=O.[O:8]=[C:9]([N:28]1[CH2:33][CH2:32][C:31]([CH2:34][C:35]2[S:36][CH:37]=[CH:38][N:39]=2)=[CH:30][CH2:29]1)/[CH:10]=[CH:11]/[C:12]1[CH:13]=[C:14]2[C:24](=[N:25][CH:26]=1)[NH:23][C:22](=[O:27])[C:16]1([CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1)[CH2:15]2.C=O.C(N(CC)CC)C.[BH4-].[Na+]>CO>[CH3:2][N:19]1[CH2:20][CH2:21][C:16]2([CH2:15][C:14]3[C:24](=[N:25][CH:26]=[C:12](/[CH:11]=[CH:10]/[C:9](=[O:8])[N:28]4[CH2:33][CH2:32][C:31]([CH2:34][C:35]5[S:36][CH:37]=[CH:38][N:39]=5)=[CH:30][CH2:29]4)[CH:13]=3)[NH:23][C:22]2=[O:27])[CH2:17][CH2:18]1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 8471TriethylamineHCID 4311764Sodium borohydrideHCID 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-trifluoroacetate

Product 1

HCID 90410367(E)-1'-methyl-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 15%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
27.5 °C

Procedure

To a stirred solution of (E)-β-methyl-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 (Compound 34) (200 mg, 0.35 mmol) in methanol (3 mL) was added 37% formaldehyde solution (0.086 mL, 1.07 mmol), followed by triethylamine (0.15 mL, 1.07 mmol) at 20-35° C. and the mixture was continued stirring at 20-35° C. for 30 minutes. Then NaBH4 (20 mg, 0.53 mmol) was added slowly portionwise at 0° C. and the reaction mixture was allowed to stir at 20-35° C. for 16 h. The reaction mixture was rotary evaporated under vacuum to get residue which was purified by preparative HPLC to get the desired compound as an off-white solid (25 mg, 15%); 1H NMR (400 MHz, DMSO-d6) δ 10.66 (s, 1H), 8.34 (s, 1H), 8.15 (s, 1H), 7.71 (d, J=2.9 Hz, 1H), 7.61 (d, J=2.5 Hz, 1H), 7.45 (d, J=15.6 Hz, 1H), 7.30-7.14 (m, 1H), 5.68-5.64 (m, 1H), 4.26-4.22 (m, 1H), 4.06-4.02 (m, 1H), 3.80-3.72 (m, 3H), 3.68-3.62 (m, 1H), 2.90 (s, 2H), 2.62-2.54 (m, 2H), 2.28-2.04 (m, 4H), 2.19 (s, 3H), 1.90-1.78 (m, 2H), 1.42-1.28 (m, 2H); LC-MS: 464.3 (M+1)+. Preparative HPLC conditions: Column-Phenomenex Luna C18 (2) (250×21.1 mm, 5μ), Mobile Phase: (A) 0.1% TFA(Aq); (B) ACN; Flow rate: 15 ml/min.

Workup

  1. stirringto stir at 20-35° C. for 16 h
  2. customThe reaction mixture was rotary evaporated under vacuum
  3. customto get residue which
  4. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-4b52d8a4f9ba4acaa954d6e4f2c9a5fa
Source dataset
uspto-grants-2015_06
Patent number
US09062075B2

Reaction notes

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