8-chloro-2-methyl-1H,2H,3H,4H,5H-pyrido(4,3-b)indole → 1-(8-Chloro-2-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-2-pyrimidin-4-yl-propan-2-ol

HRID 1773279Notes

Reaction equation

HRID 1773279 reaction equation
[H-].[Na+].[CH3:3][N:4]1[CH2:17][CH2:16][C:7]2[NH:8][C:9]3[CH:10]=[CH:11][C:12]([Cl:15])=[CH:13][C:14]=3[C:6]=2[CH2:5]1.[CH3:18][C:19]1([C:22]2[CH:27]=[CH:26][N:25]=[CH:24][N:23]=2)[CH2:21][O:20]1>CCCCCC.CN(C=O)C>[Cl:15][C:12]1[CH:11]=[CH:10][C:9]2[N:8]([CH2:18][C:19]([C:22]3[CH:27]=[CH:26][N:25]=[CH:24][N:23]=3)([OH:20])[CH3:21])[C:7]3[CH2:16][CH2:17][N:4]([CH3:3])[CH2:5][C:6]=3[C:14]=2[CH:13]=1

Participants

6

Reactant 3

HCID 196158-chloro-2-methyl-1H,2H,3H,4H,5H-pyrido(4,3-b)indoleHCID 24758Sodium hydrideHCID 594549674-(2-Methyloxiran-2-yl)pyrimidine

Product 1

HCID 497794421-(8-Chloro-2-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-2-pyrimidin-4-yl-propan-2-ol

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8058HexaneSolvent

Procedure

Sodium hydride (275 mg, 11.45 mmol) was washed with hexane and dried under vacuum. DMF (4 mL) was added, resulting in a suspension. 2,3,4,5-Tetrahydro-2-methyl-8-chloro-1H-pyrido[4,3-b]indole (500 mg, 2.27 mmol) dissolved in DMF (2 mL) was added dropwise and the reaction mixture stirred for 30 min at RT. 4-(2-Methyl-oxiranyl)-pyrimidine (620 mg, 4.55 mmol) dissolved in DMF (2 mL) was added dropwise and the reaction mixture was stirred overnight at RT. The progress of reaction was monitored by TLC. The mixture was quenched with ice-cold water and the mixture extracted with EtOAc (3×30 mL). The combined organic layer was washed with water (4×20 mL) followed by brine (1×20 mL), dried over sodium sulfate and the solvent evaporated under vacuum. The residue was washed with hexane and crystallized from ether: DCM and hexane. 1HNMR (CD3OD, Oxalate salt) d (ppm): 9.10 (s, 1H), 8.50 (d, 1H), 7.50 (d, 1H), 7.36 (s, 1H), 7.10 (d, 1H), 6.95 (d, 1H), 4.40 (m, 4H), 3.60 (m, 2H), 3.40 (m, 1H), 3.20 (m, 1H), 3.05 (s, 3H), 1.60 (s, 3H).

Workup

  1. customdried under vacuum
  2. additionDMF (4 mL) was added
  3. customresulting in a suspension
  4. additionwas added dropwise
  5. additionwas added dropwise
  6. stirringthe reaction mixture was stirred overnight at RT
  7. customThe progress of reaction
  8. customThe mixture was quenched with ice-cold water
  9. extractionthe mixture extracted with EtOAc (3×30 mL)
  10. washThe combined organic layer was washed with water (4×20 mL)
  11. dry with materialdried over sodium sulfate
  12. customthe solvent evaporated under vacuum
  13. washThe residue was washed with hexane
  14. customcrystallized from ether

Sources & evidence

ORD record
ord-03620e0199b048c4b07ac6750524f982
Source dataset
uspto-grants-2016_02
Patent number
US09255094B2

Reaction notes

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