2-Quinolinecarboxaldehyde → HCID 66932339, compound

HRID 518222Notes

Reaction equation

HRID 518222 reaction equation
[CH3:1][O:2][C:3](=[O:29])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[C:8]2[C:25](=[CH:26][CH:27]=1)[O:24][C:11]1([CH2:16][CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13][CH2:12]1)[CH2:10][C:9]2=[O:28].[N:30]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH:33]=[CH:32][C:31]=1[CH:40]=O.[Na]>C([O-])([O-])=O.[Na+].[Na+]>[CH3:1][O:2][C:3](=[O:29])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[C:8]2[C:25](=[CH:26][CH:27]=1)[O:24][C:11]1([CH2:12][CH2:13][N:14]([CH2:40][C:31]3[CH:32]=[CH:33][C:34]4[C:39](=[CH:38][CH:37]=[CH:36][CH:35]=4)[N:30]=3)[CH2:15][CH2:16]1)[CH2:10][C:9]2=[O:28]

Participants

5

Reactant 3

HCID 796192-QuinolinecarboxaldehydeHCID 5360545SodiumHCID 52952087(E)-3-{1'-tert-butoxycarbonyl-4-oxo-spiro[chromane-2,4'-piperidine]-6-yl}-acrylic acid methyl ester2×

Product 1

HCID 66932339HCID 66932339, compoundYield 88.6%

Reagents, catalysts & solvents 1

HCID 10340Sodium CarbonateSolvent

Procedure

A suspension of (E)-3-{4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester (169 mg, 0.500 mmol, Intermediate 1, hydrochloride salt) in 1 M Na2CO3, was stirred for 10 minutes, then extracted with DCM and treated with quinoline-2-carbaldehyde (96 mg, 0.61 mmol) and sodium triacethoxyborohydride (159 mg, 0.750 mmol) following the procedure described in Example 55, Step A, giving (E)-3-{1′-(quinolin-2-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester (196 mg) as a yellow solid. The ester was hydrolyzed as described in Example 55, Step B, giving (E)-3-{1′-(quinolin-2-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid (190 mg) as an orange solid (hydrochloride salt). The acid was suspended in DCM (5 ml), TEA (0.16 ml, 1.16 mmol) was added, and the clear solution was treated with NH2OTHP following the procedure described in Example 1, Step B, giving (E)-3-{1′-(quinolin-2-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide (162 mg) as a yellow solid. The compound was then was dissolved in DCM (5 ml) and treated with 4 M HCl in dioxane (0.4 ml, 1.6 mmol) as described in Example 55, Step D, giving a yellow solid (145 mg, di-hydrochloride salt)

Workup

  1. extractionextracted with DCM

Sources & evidence

ORD record
ord-1953ff486bcb40238d183d33e066b0b3
Source dataset
uspto-grants-2015_08
Patent number
US09115148B2

Reaction notes

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