4-Aminotetrahydropyran → HCID 86696735, compound

HRID 2365880Notes

Reaction equation

HRID 2365880 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([N:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[CH:31][N:30]=[C:29](S(C)(=O)=O)[N:28]=3)=[CH:23][C:22]2=[O:37])[C@@H:9]2[CH2:13][CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10]2)=[CH:4][C:3]=1[F:38].[O:39]1[CH2:44][CH2:43][CH:42]([NH2:45])[CH2:41][CH2:40]1>CC(N(C)C)=O.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([C@@H:9]2[CH2:13][CH2:12][NH:11][CH2:10]2)[N:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[CH:31][N:30]=[C:29]([NH:45][CH:42]4[CH2:43][CH2:44][O:39][CH2:40][CH2:41]4)[N:28]=3)=[CH:23][C:22]2=[O:37])=[CH:4][C:3]=1[F:38]

Participants

5

Reactant 2

HCID 4192234-AminotetrahydropyranHCID 86696736HCID 86696736, compound

Product 1

HCID 86696735HCID 86696735, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

(R)-tert-Butyl 3-((R)-(4-chloro-3-fluorophenyl)(4-(2-(methylsulfonyl)pyrimidin-4-yl)-2-oxopyridin-1(2H)-yl)methyl)pyrrolidine-1-carboxylate (45.1 mg, 0.0801 mmol) was dissolved in DMA (1.0 mL, 0.1M) at room temperature under nitrogen and treated with tetrahydro-2H-pyran-4-amine (40.5 mg, 0.401 mmol). The solution was heated to 120° C. for 1 hour in the microwave. The reaction was then diluted with EtOAc (15 mL) and washed with water (3×15 mL) and brine (15 mL). The organics were isolated, dried over sodium sulfate, filtered and concentrated. The crude product was loaded onto an SP1 samplet and purified by silica gel chromatography using a 10% to 80% gradient of acetone in hexanes. Product containing fractions were pooled, concentrated and then redissolved in dichloromethane (2 mL) and treated with 1:1 TFA/DCM (1.0 mL) and stirred at room temperature for 1 hour. The reaction was diluted to 15 mL with additional DCM and washed with NaHCO3 (2×15 mL). The organics were isolated, dried over sodium sulfate, filtered and concentrated to afford 1-((R)-(4-chloro-3-fluorophenyl)((R)-pyrrolidin-3-yl)methyl)-4-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one as an oil. 1H NMR (400 MHz, ((CD3)2SO) δ 8.40 (d, 1H), 8.04 (d, 1H), 7.62 (m, 2H), 7.37 (d, 1H), 7.34 (br s, 1H), 7.13 (d, 1H), 7.08 (s, 1H), 6.86 (d, 1H), 5.84 (br s, 1H), 3.97 (m, 1H), 3.87 (m, 2H), 3.38 (m, 2H), 2.86 (m, 1H), 2.79 (m, 2H), 2.34 (m, 1H), 1.84 (br d, 2H), 1.74 (m, 1H), 1.52 (m, 3H), 1.27 (m, 2H); LCMS (ESI) m/z 484.1 [M+H+].

Workup

  1. washwashed with water (3×15 mL) and brine (15 mL)
  2. customThe organics were isolated
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by silica gel chromatography
  7. additionProduct containing fractions
  8. concentrationconcentrated
  9. dissolutionredissolved in dichloromethane (2 mL)
  10. additiontreated with 1:1 TFA/DCM (1.0 mL)
  11. additionThe reaction was diluted to 15 mL with additional DCM
  12. washwashed with NaHCO3 (2×15 mL)
  13. customThe organics were isolated
  14. dry with materialdried over sodium sulfate
  15. filtrationfiltered
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-d9bfaa74f5654243b0fabab3872703f0
Source dataset
uspto-grants-2014_04
Patent number
US08697715B2

Reaction notes

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