Acetic Acid → N-[1-(cyclobutylmethyl)-3-methylpyrrolidin-3-yl]-N-[(1-methyl-2-oxo-1,2-dihydroquinolin-3-yl)methyl]cyclohexanecarboxamide

HRID 1943032Notes

Reaction equation

HRID 1943032 reaction equation
[CH3:1][N:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([CH2:12][N:13]([C:22]2([CH3:27])[CH2:26][CH2:25][NH:24][CH2:23]2)[C:14]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)=[O:15])[C:3]1=[O:28].[CH:29]1([CH:33]=O)[CH2:32][CH2:31][CH2:30]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH:29]1([CH2:33][N:24]2[CH2:25][CH2:26][C:22]([N:13]([CH2:12][C:4]3[C:3](=[O:28])[N:2]([CH3:1])[C:11]4[C:6]([CH:5]=3)=[CH:7][CH:8]=[CH:9][CH:10]=4)[C:14]([CH:16]3[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)=[O:15])([CH3:27])[CH2:23]2)[CH2:32][CH2:31][CH2:30]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 12431621CyclobutanecarbaldehydeHCID 58415934N-[(1-methyl-2-oxo-1,2-dihydroquinolin-3-yl)methyl]-N-(3-methylpyrrolidin-3-yl)cyclohexanecarboxamide

Product 1

HCID 58415936N-[1-(cyclobutylmethyl)-3-methylpyrrolidin-3-yl]-N-[(1-methyl-2-oxo-1,2-dihydroquinolin-3-yl)methyl]cyclohexanecarboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-[(1-methyl-2-oxo-1,2-dihydroquinolin-3-yl)methyl]-N-(3-methylpyrrolidin-3-yl)cyclohexanecarboxamide (300 mg, 0.786 mmol), cyclobutanecarbaldehyde (99 mg, 1.180 mmol), and acetic acid (0.090 ml, 1.573 mmol) were combined in CH2Cl2 (70 ml). Sodium triacetoxyborohydride (333 mg, 1.573 mmol) was added and the reaction stirred for 2.5 hours. The reaction mixture was partitioned between CH2Cl2 and satd. bicarb, the aqueous portion extracted 3×CH2Cl2, and the organic portion dried (Na2SO4) then concentrated in vacuo. The resulting material was purified in two batches by reversed phase chromatography (15-95% ACN in water (with 0.5 ml/l NH4OH) over 20 min at 50 ml/min, 30×100 mm Phenomenex Gemini C18 column). Desired fractions were combined and concentrated in vacuo. HRMS [M+H]1+ 450.3099. 1H NMR (400 MHz, CDCl3): δ 7.62-7.55 (m, 3 H); 7.42 (d, J=8.5 Hz, 1 H); 7.29 (t, J=7.6 Hz, 1 H); 4.44 (s, 2 H); 3.80 (s, 3 H); 2.99 (d, J=10.0 Hz, 1 H); 2.85 (d, J=10.2 Hz, 1 H); 2.53 (t, J=7.9 Hz, 1 H); 2.47-2.35 (m, 4 H); 2.09-1.92 (m, 5 H); 1.92-1.64 (m, 14 H); 1.28-0.99 (m, 3 H). 210 mg, 59%.

Workup

  1. customThe reaction mixture was partitioned between CH2Cl2 and satd
  2. extractionbicarb, the aqueous portion extracted 3×CH2Cl2
  3. dry with materialthe organic portion dried (Na2SO4)
  4. concentrationthen concentrated in vacuo
  5. customThe resulting material was purified in two batches by reversed phase chromatography (15-95% ACN in water (with 0.5 ml/l NH4OH) over 20 min at 50 ml/min, 30×100 mm Phenomenex Gemini C18 column)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-157e1be0a62845438cdf1b9761bcccfe
Source dataset
uspto-grants-2013_03
Patent number
US08389720B2

Reaction notes

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