p-Toluidine → HCID 68290942, compound

HRID 2205865Notes

Reaction equation

HRID 2205865 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[CH:15]=[C:14](Cl)[N:13]=[CH:12][C:11]=2[CH:10]=[C:9]1[C:18]1[CH:19]=[N:20][N:21]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH:22]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:30][C:31]1[CH:37]=[CH:36][C:34]([NH2:35])=[CH:33][CH:32]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.CN1C(=O)CCC1>[C:26]([O:25][C:23]([N:21]1[CH:22]=[C:18]([C:9]2[N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[C:16]3[CH:15]=[C:14]([NH:35][C:34]4[CH:36]=[CH:37][C:31]([CH3:30])=[CH:32][CH:33]=4)[N:13]=[CH:12][C:11]=3[CH:10]=2)[CH:19]=[N:20]1)=[O:24])([CH3:29])([CH3:28])[CH3:27]

Participants

8

Reactant 4

HCID 7813p-ToluidineHCID 62657Potassium Phosphate, TribasicHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86706279HCID 86706279, compound

Product 1

HCID 68290942HCID 68290942, compoundYield 33.1%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent2×HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

tert-Butyl-2-(1-(tert-butoxycarbonyl)-1H-pyrazol-4-yl)-6-chloro-1H-pyrrolo[3,2-c]pyridine-1-carboxylate (17) (44 mg 0.105 mmole) and 4-methylaniline (13 mg 0.12 mmole) were placed in a microwave vial and potassium phosphate (53 mg 0.25 mmole), XantPhos (10.5 mg 0.022 mmol) and Pd2(dba)3 (10.1 mg 0.011 mmol) were added. NMP containing water (3%) (1.2 mL) was then added and the vial sealed under argon. It was microwaved at 80° C. for 1.5 hrs. The reaction was added to water (10 mL) and extracted with ethyl acetate (3×6 mL). The combined organics were washed with water (3×5 mL) and with brine, dried and evaporated. The residue was applied to three 1 mm 20×20 cm silica prep tlc plates, which were twice eluted with 1:2 ethyl acetate:cyclohexane. The product band was recovered using acetone to give the product (17 mg). 1H-NMR (CDCl3, 500 MHz): δ 1.51 (s, 9H), 1.70 (s, 9H), 2.36 (s, 3H), 6.58 (m, 1H), 6.68 (br s, 1H, NH), 7.18 (d, J=8.20 Hz, 1H), 7.25 (d, J=8.51 Hz, 2H), 7.54 (m, 1H), 7.83 (d, J=0.63 Hz, 1H), 8.23 (s, 1H), 8.44 (m, 1H). ESI-HRMS Found 490.2452, calculated for C27H32N5O4 [M+H]+: 490.2449.

Workup

  1. additionwere added
  2. additionwas then added
  3. customthe vial sealed under argon
  4. customIt was microwaved at 80° C. for 1.5 hrs
  5. extractionextracted with ethyl acetate (3×6 mL)
  6. washThe combined organics were washed with water (3×5 mL) and with brine
  7. customdried
  8. customevaporated
  9. washwere twice eluted with 1:2 ethyl acetate
  10. customThe product band was recovered

Sources & evidence

ORD record
ord-087f89c73dfe4f928ff678e14247f253
Source dataset
uspto-grants-2016_06
Patent number
US09371319B2

Reaction notes

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