Potassium Phosphate, Tribasic → HCID 86706299, compound

HRID 2205886Notes

Reaction equation

HRID 2205886 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].P([O-])([O-])([O-])=O.[K+].[K+].[K+].[NH2:38][C:39]1[CH:49]=[CH:48][C:42]([C:43]([N:45]([CH3:47])[CH3:46])=[O:44])=[CH:41][CH:40]=1>C(O)(C)(C)C.[Pd].C(OCC)(=O)C.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]>[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:38][C:39]4[CH:40]=[CH:41][C:42]([C:43](=[O:44])[N:45]([CH3:46])[CH3:47])=[CH:48][CH:49]=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 3

HCID 62657Potassium Phosphate, TribasicHCID 2355274-Amino-N,N-dimethylbenzamideHCID 86706279HCID 86706279, compound

Product 1

HCID 86706299HCID 86706299, compoundYield 35.3%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalyst2×HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6386tert-ButanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Pd2(dba)3 (11.32 mg, 0.012 mmol) was added to a mixture of tert-butyl 2-(1-(tert-butoxycarbonyl)-1H-pyrazol-4-yl)-6-chloro-1H-pyrrolo[3,2-c]pyridine-1-carboxylate (17) (37 mg, 0.088 mmol), potassium phosphate (62.1 mg, 0.29 mmol), 4-amino-N,N-dimethylbenzamide (16.68 mg, 0.10 mmol) and di-tBuX-Phos (15.75 mg, 0.037 mmol) in tert-BuOH containing 3% water (1.0 mL). The reaction mixture was heated at 80° C. for 1 h under microwave irradiation. More palladium catalyst (10.0 mg) and di-tBuX-Phos (8.0 mg) were added and the reaction mixture was heated at 80° C. for an additional 70 min under microwave irradiation. A final portion of palladium catalyst (4.0 mg) was added and the reaction mixture was heated at 80° C. for 70 min under microwave irradiation; it was then diluted with ethyl acetate (40 mL), washed with water (2×10 mL), dried (Na2SO4), and concentrated in vacuo. The residue was absorbed on silica gel (0.7 g), the free-running powder was placed on a 10 g isolute silica column. Elution with 60%, 70%, 80%, 90% ethyl acetate in hexane afforded the title compound (0.017 g) that was contaminated with the aniline starting material (4-amino-N,N-dimethylbenzamide) in a ratio of 1:1. 1H-NMR (500 MHz, CDCl3) 1.53 (s, 9H), 1.69 (s, 9H), 3.10 (s, 6H), 6.60 (d, J=0.6 Hz), 6.73 (br s, 1H), 7.39 (d, J=8.6 Hz, 2H), 7.45 (d, J=8.6 Hz, 2H), 7.70 (s, 1H), 7.83 (d, J=0.7 Hz, 1H), 8.23 (d, J=0.6 Hz, 1H), 8.50 (d, J=0.8 Hz, 1H). Also present were the following peaks consistent with the structure of the starting material, 4-amino-N,N-dimethylbenzamide: 3.06 (s, 6H), 3.84 (br s, 2H), 6.66 (d, J=8.6 Hz, 2H), 7.30 (d, J=8.6 Hz, 2H).

Workup

  1. temperaturethe reaction mixture was heated at 80° C. for an additional 70 min under microwave irradiation
  2. temperaturethe reaction mixture was heated at 80° C. for 70 min under microwave irradiation
  3. washwashed with water (2×10 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe residue was absorbed on silica gel (0.7 g)
  7. washElution with 60%, 70%, 80%, 90% ethyl acetate in hexane

Sources & evidence

ORD record
ord-c4ee0c74a52d49f594bff0bc453fea5c
Source dataset
uspto-grants-2016_06
Patent number
US09371319B2

Reaction notes

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