4-Aminotetrahydropyran → HCID 71727471, compound

HRID 1774200Notes

Reaction equation

HRID 1774200 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:26]2[O:30][CH:29]=[N:28][CH:27]=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:31].[O:32]1[CH2:37][CH2:36][CH:35]([NH2:38])[CH2:34][CH2:33]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[O:30][CH:29]=[N:28][CH:27]=2)[N:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][N:18]=[C:17]([NH:38][CH:35]4[CH2:36][CH2:37][O:32][CH2:33][CH2:34]4)[N:16]=3)=[CH:11][C:10]2=[O:25])=[CH:4][C:3]=1[F:31]

Participants

5

Reactant 2

HCID 4192234-AminotetrahydropyranHCID 86696700HCID 86696700, compound

Product 1

HCID 71727471HCID 71727471, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

A microwave tube was charged with a solution of 1-((4-chloro-3-fluorophenyl)(oxazol-5-yl)methyl)-4-(2-(methylsulfonyl)pyrimidin-4-yl)pyridin-2(1H)-one (53 mg, 0.12 mmol) in DMA (1.2 mL). Tetrahydro-2H-pyran-4-amine (35 mg, 0.35 mmol) was added neat by syringe. The reaction was put into a microwave apparatus and heated to 120° C. 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 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 12M column with ethyl acetate and eluted. Product containing fractions were pooled and concentrated to an oil, 1-((4-chloro-3-fluorophenyl)(oxazol-5-yl)methyl)-4-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (20 mg, 36%). 1H NMR (400 MHz, CDCl3) 8.40 (d, 1H), 7.98 (s, 1H), 7.56 (s, 1H), 7.43 (dd, 1H), 7.31 (d, 1H), 7.22 (br s, 1H), 7.08 (s, 1H), 7.00 (m, 2H), 6.90 (s, 1H), 6.83 (dd, 1H), 5.20 (br d, 1H), 4.11 (m, 1H), 4.01 (m 2H), 3.55 (m, 2H), 2.06 (m, 2H), 1.58 (m, 2H); m/z (APCI-pos) M+1=483.0.

Workup

  1. washwashed with a water/brine mixture (4×30 mL)
  2. customThe organics were isolated
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. washeluted
  7. additionProduct containing fractions
  8. concentrationconcentrated to an oil, 1-((4-chloro-3-fluorophenyl)(oxazol-5-yl)methyl)-4-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (20 mg, 36%)

Sources & evidence

ORD record
ord-d1e887d7931a460e9cb03ed1f15e2cf1
Source dataset
uspto-grants-2016_02
Patent number
US09259470B2

Reaction notes

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