Diisopropylethylamine → 1-Methyl-piperidine-4-carboxylic acid [2-(2-methoxy-benzylamino)-quinolin-6-yl]-amide

HRID 1803078

Reaction equation

HRID 1803078 reaction equation
Cl.[CH3:2][N:3]1[CH2:8][CH2:7][CH:6]([C:9]([OH:11])=O)[CH2:5][CH2:4]1.C(N(C(C)C)C(C)C)C.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:55][O:56][C:57]1[CH:75]=[CH:74][CH:73]=[CH:72][C:58]=1[CH2:59][NH:60][C:61]1[CH:70]=[CH:69][C:68]2[C:63](=[CH:64][CH:65]=[C:66]([NH2:71])[CH:67]=2)[N:62]=1.C(=O)(O)[O-].[Na+]>O1CCCC1>[CH3:55][O:56][C:57]1[CH:75]=[CH:74][CH:73]=[CH:72][C:58]=1[CH2:59][NH:60][C:61]1[CH:70]=[CH:69][C:68]2[C:63](=[CH:64][CH:65]=[C:66]([NH:71][C:9]([CH:6]3[CH2:5][CH2:4][N:3]([CH3:2])[CH2:8][CH2:7]3)=[O:11])[CH:67]=2)[N:62]=1

Participants

8

Reactant 6

HCID 81531Diisopropylethylamine2×HCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27600434-Piperidinecarboxylic acid, 1-methyl-, hydrochloride (1:1)HCID 43450845N2-(2-Methoxy-benzyl)-quinoline-2,6-diamine

Product 1

HCID 866344211-Methyl-piperidine-4-carboxylic acid [2-(2-methoxy-benzylamino)-quinolin-6-yl]-amideYield 48.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 1-methyl-piperidine-4-carboxylic acid hydrochloride salt (35 mg, 179 mmol) in tetrahydrofurane (3 ml) were added at room temperature N-ethyldiisopropylamine (74 mg, 0.573 mmol), 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (27 mg, 0.197 mmol), N,N-diisopropyl ethyl amine (74 mg, 0.197 mmol) and 1-(3-dimethylamino-propyl)-3-ethylcarbodiimide hydrochloride (38 mg, 0.197 mmol) and the mixture was allowed to stir for 90 min. N2-(2-Methoxy-benzyl)-quinoline-2,6-diamine (example 10, step B, 50 mg, 0.179 mmol) was added and the reaction mixture was allowed to stir for 17 h, poured into sat. sodium bicarbonate solution (30 ml) and extracted with dichloromethane (2×30 ml). The combined organic layers were washed with water (30 ml), dried (MgSO4) and evaporated. The crude product was further purified by flash chromatography on silica gel (heptane/ethyl acetate) and crystallization (ethyl acetate/heptane) to yield the title compound as white solid (35 mg, 48%). MS: m/e=405.5 (M+H+).

Workup

  1. stirringto stir for 17 h
  2. extractionextracted with dichloromethane (2×30 ml)
  3. washThe combined organic layers were washed with water (30 ml)
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customThe crude product was further purified by flash chromatography on silica gel (heptane/ethyl acetate) and crystallization (ethyl acetate/heptane)

Sources & evidence

ORD record
ord-4d48e4bd7fbe4e64b5a0cbe33b7701ed
Source dataset
uspto-grants-2013_01
Patent number
US08350028B2

Linked notes

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