4-Aminotetrahydropyran → HCID 71727472, compound

HRID 1774201Notes

Reaction equation

HRID 1774201 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:26]2[CH:27]=[N:28][N:29]([CH3:31])[CH:30]=2)[N:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][N:18]=[C:17](S(C)(=O)=O)[N:16]=3)=[CH:11][C:10]2=[O:25])=[CH:4][C:3]=1[F:32].[O:33]1[CH2:38][CH2:37][CH:36]([NH2:39])[CH2:35][CH2:34]1>CC(N(C)C)=O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:26]2[CH:27]=[N:28][N:29]([CH3:31])[CH:30]=2)[N:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][N:18]=[C:17]([NH:39][CH:36]4[CH2:37][CH2:38][O:33][CH2:34][CH2:35]4)[N:16]=3)=[CH:11][C:10]2=[O:25])=[CH:4][C:3]=1[F:32]

Participants

5

Reactant 2

HCID 4192234-AminotetrahydropyranHCID 86696701HCID 86696701, compound

Product 1

HCID 71727472HCID 71727472, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

1-((4-Chloro-3-fluorophenyl)(1-methyl-1H-pyrazol-4-yl)methyl)-4-(2-(methylsulfonyl)pyrimidin-4-yl)pyridin-2(1H)-one (343 mg, 0.724 mmol) as a solution in DMA (5 mL) was added to a microwave tube equipped with a stir bar. Tetrahydro-2H-pyran-4-amine (366 mg, 3.62 mmol) was then added neat by syringe. The solution was heated in a microwave apparatus with stirring to 120° C. for 1 hour. After 1 hour, the solution was diluted to 30 mL with ethyl acetate and washed with a water/brine mixture (4×30 mL). The organics were isolated, dried (MgSO4), filtered and concentrated. TLC in 5/95 methanol/ethyl acetate showed complete loss of starting material and a new spot of nearly the same rf. The crude product was loaded onto a Biotage 40S column with 2.5/97.5 methanol/ethyl acetate and eluted. Product containing fractions were pooled and concentrated to a foam, 1-((4-chloro-3-fluorophenyl)(1-methyl-1H-pyrazol-4-yl)methyl)-4-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (225 mg, 63%). 1H NMR (400 MHz, CDCl3) δ 8.39 (d, 1H), 7.37 (m, 4H), 7.23 (s, 1H), 7.18 (br s, 1H), 7.00 (m, 2H), 6.90 (d, 1H), 6.79 (dd, 1H), 5.15 (br d, 1H), 4.11 (m, 1H), 4.00 (m, 2H), 3.91 (s, 3H), 3.56 (m, 2H), 2.06 (m, 2H), 1.57 (m, 2H); m/z (APCI-pos) M+1=496.1.

Workup

  1. customequipped with a stir bar
  2. temperatureThe solution was heated in a microwave apparatus
  3. waitAfter 1 hour
  4. washwashed with a water/brine mixture (4×30 mL)
  5. customThe organics were isolated
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. washeluted
  10. additionProduct containing fractions
  11. concentrationconcentrated to a foam, 1-((4-chloro-3-fluorophenyl)(1-methyl-1H-pyrazol-4-yl)methyl)-4-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (225 mg, 63%)

Sources & evidence

ORD record
ord-3b2c8aefc41a4541907f4af68fecc8ed
Source dataset
uspto-grants-2016_02
Patent number
US09259470B2

Reaction notes

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