2-Methyl-2-butene → 6-chloro-5-[2-(morpholin-4-yl)pyrimidin-5-yl]-1H-indole-3-carboxylic acid

HRID 1054750Notes

Reaction equation

HRID 1054750 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:14]=[N:15][C:16]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)=[N:17][CH:18]=1.CC(=CC)C.Cl([O-])=[O:31].[Na+].O.O.OP([O-])(O)=O.[Na+]>C(#N)C.O.C(O)(C)(C)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:31])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:14]=[N:15][C:16]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)=[N:17][CH:18]=1

Participants

8

Reactant 4

HCID 105532-Methyl-2-buteneHCID 23668197Sodium ChloriteHCID 23673460Sodium Phosphate, Monobasic, DihydrateHCID 866987436-chloro-5-[2-(morpholin-4-yl)pyrimidin-5-yl]-1H-indole-3-carbaldehyde

Product 1

HCID 866987446-chloro-5-[2-(morpholin-4-yl)pyrimidin-5-yl]-1H-indole-3-carboxylic acidYield 40.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
0 °C

Procedure

6-chloro-5-[2-(morpholin-4-yl)pyrimidin-5-yl]-1H-indole-3-carbaldehyde (159 mg, 0.464 mmol) was dissolved in acetonitrile (6 mL) and warm tert-butanol (6 mL) and treated with 2-methyl-2-butene. The reaction mixture was cooled to 0° C. and treated with a solution of sodium chlorite (630 mg, 9.27 mmol) and sodium phosphate monobasic dihydrate (1.45 g, 9.30 mmol) in water (5 mL) via addition funnel. The mixture was stirred at room temperature overnight. The reaction mixture was then concentrated in vacuo to remove the organics and extracted with EtOAc (3×20 mL). The combined organics were washed with brine (20 mL), dried and concentrated in vacuo to give a crude, which was purified by prep-HPLC to give 6-chloro-5-[2-(morpholin-4-yl)pyrimidin-5-yl]-1H-indole-3-carboxylic acid (67.6 mg, 40.60% yield) as a white solid. MS (ES+) 359.1 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 12.22 (s, 1 H), 12.03 (s, 1 H), 8.49 (m, 2 H), 8.12 (m, 1 H), 7.97 (s, 1 H), 7.69 (s, 1 H), 3.78 (m, 4 H), 3.70 (m, 4 H).

Workup

  1. concentrationThe reaction mixture was then concentrated in vacuo
  2. customto remove the organics and
  3. extractionextracted with EtOAc (3×20 mL)
  4. washThe combined organics were washed with brine (20 mL)
  5. customdried
  6. concentrationconcentrated in vacuo
  7. customto give a crude, which
  8. customwas purified by prep-HPLC

Sources & evidence

ORD record
ord-96d327b17b1540b992af057c2a55d723
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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