Cyclopropylamine → HCID 86675923, compound

HRID 572668Notes

Reaction equation

HRID 572668 reaction equation
[F:1][C:2]1[CH:34]=[CH:33][C:5]([CH2:6][NH:7][C:8]([C:10]2[N:15]=[C:14]([CH3:16])[N:13]=[C:12]([C:17]3[CH2:21][CH:20]([C:22]4[CH:23]=[CH:24][C:25](=[O:32])[N:26]([CH2:28][C:29]([OH:31])=O)[CH:27]=4)[O:19][N:18]=3)[CH:11]=2)=[O:9])=[CH:4][C:3]=1[O:35][CH3:36].[CH:37]1([NH2:40])[CH2:39][CH2:38]1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH:37]1([NH:40][C:29](=[O:31])[CH2:28][N:26]2[C:25](=[O:32])[CH:24]=[CH:23][C:22]([CH:20]3[O:19][N:18]=[C:17]([C:12]4[N:13]=[C:14]([CH3:16])[N:15]=[C:10]([C:8]([NH:7][CH2:6][C:5]5[CH:33]=[CH:34][C:2]([F:1])=[C:3]([O:35][CH3:36])[CH:4]=5)=[O:9])[CH:11]=4)[CH2:21]3)=[CH:27]2)[CH2:39][CH2:38]1

Participants

7

Reactant 5

HCID 69828CyclopropylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86675924HCID 86675924, compound

Product 1

HCID 86675923HCID 86675923, compoundYield 9.73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution 2-(5-(3-(6-(4-fluoro-3-methoxybenzylcarbamoyl)-2-methylpyrimidin-4-yl)-4,5-dihydroisoxazol-5-yl)-2-oxopyridin-1(2H)-yl)acetic acid (0.2 g, 0.404 mmol, G.1.225) in DMF (5 mL) was added cyclopropanamine (0.046 g, 0.807 mmol, Sd Fine Chem), EDCI.HCl (0.093 g, 0.484 mmol, spectrochem), HOBT (0.093 g, 0.605 mmol, spectrochem) and DIPEA (0.157 g, 1.211 mmol, spectrochem). The reaction mixture was stirred at RT for about 12 h. The reaction mixture was diluted with ice cold water (20 mL) and the product extracted with EtOAc (2×15 mL), The organic layer was dried over sodium sulphate and evaporated under reduced pressure to afford a thick mass. Crude compound was purified by preparative TLC, eluting with 2-4% methanol in DCM to afford 6-(5-(1-(2-(cyclopropylamino)-2-oxoethyl)-6-oxo-1,6-dihydropyridin-3-yl)-4,5-dihydroisoxazol-3-yl)-N-(4-fluoro-3-methoxybenzyl)-2-methylpyrimidine-4-carboxamide 21 mg (9.73%) as an off white solid. 1H NMR (400 MHz, DMSO): δ 9.519-9.487 (m, 1H), 8.282-8.273 (d, J=3.6 Hz, 1H), 8.190 (s, 1H), 7.768-7.762 (d, J=2.4 Hz, 1H), 7.558-7.529 (dd, J=9.2 Hz, 1H), 7.186-7.119 (m, 2H), 6.908-6.871 (m, 1H), 6.429-6.404 (d, J=10 Hz, 1H), 5.705-5.654 (m, 1H), 4.491-4.458 (m, 4H), 3.857-3.784 (m, 4H), 3.461-3.393 (m, 1H), 2.767 (s, 3H), 2.745-2.650 (m, 1H), 0.649-0.601 (m, 2H) 0.425-0.387 (m, 2H); MS m/z=533.3 (M−H)−.

Workup

  1. extractionthe product extracted with EtOAc (2×15 mL)
  2. dry with materialThe organic layer was dried over sodium sulphate
  3. customevaporated under reduced pressure
  4. customto afford a thick mass
  5. customCrude compound was purified by preparative TLC
  6. washeluting with 2-4% methanol in DCM

Sources & evidence

ORD record
ord-9ab183ac7be548b89c4b55e87108edc5
Source dataset
uspto-grants-2015_05
Patent number
US09029409B2

Reaction notes

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