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

HRID 1054743Notes

Reaction equation

HRID 1054743 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]([CH3:21])[CH3:20])=[N:17][CH:18]=1.CC(=CC)C.Cl([O-])=[O:28].[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:28])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:14]=[N:15][C:16]([N:19]([CH3:21])[CH3:20])=[N:17][CH:18]=1

Participants

8

Reactant 4

HCID 105532-Methyl-2-buteneHCID 23668197Sodium ChloriteHCID 23673460Sodium Phosphate, Monobasic, DihydrateHCID 866987386-chloro-5-[2-(dimethylamino)pyrimidin-5-yl]-1H-indole-3-carbaldehyde

Product 1

HCID 866987396-chloro-5-[2-(dimethylamino)pyrimidin-5-yl]-1H-indole-3-carboxylic acidYield 41%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
0 °C

Procedure

6-chloro-5-[2-(dimethylamino)pyrimidin-5-yl]-1H-indole-3-carbaldehyde (100 mg, 0.333 mmol) was dissolved in acetonitrile (6 mL) and warm tert-butanol (6 mL) and treated with 2-methyl-2-butene (4 mL). The reaction mixture was cooled to 0° C. and treated with a solution of sodium chlorite (450 mg, 6.65 mmol) and sodium phosphate monobasic dihydrate (1.04 g, 6.65 mmol) in water (3 mL) dropwise via addition funnel. The reaction mixture was warmed to room temperature and stirred for 20 hours. The reaction mixture was concentrated to remove the organics and extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine (20 mL), dried and concentrated in vacuo. The crude product was purified by prep-HPLC (Column: Agella venusil ASB C18 150×21.2 mm×5 μm; Mobile phase: from 20% MeCN in water (0.1% HCl) to 45% MeCN in water (0.1% HCl) Wavelength: 220 nm) to give 6-chloro-5-[2-(dimethylamino)pyrimidin-5-yl]-1H-indole-3-carboxylic acid (43 mg, 41% yield) as a yellow solid. MS (ES+) 316.9 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 11.98 (s, 1 H), 8.42 (s, 2 H), 8.08 (d, 1 H), 7.93 (s, 1 H), 7.65 (s, 1 H), 3.17 (s, 6 H).

Workup

  1. temperatureThe reaction mixture was warmed to room temperature
  2. concentrationThe reaction mixture was concentrated
  3. customto remove the organics and
  4. extractionextracted with EtOAc (3×20 mL)
  5. washThe combined organic layers were washed with brine (20 mL)
  6. customdried
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by prep-HPLC (Column: Agella venusil ASB C18 150×21.2 mm×5 μm; Mobile phase: from 20% MeCN in water (0.1% HCl) to 45% MeCN in water (0.1% HCl) Wavelength: 220 nm)

Sources & evidence

ORD record
ord-03ec83937aa74925ae4e1a1c61157dcc
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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