Water → tert-Butyl 4-(6-(5-fluoropyridin-2-ylamino)-1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazole-1-carboxylate

HRID 2205891Notes

Reaction equation

HRID 2205891 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]2[CH:8]=[C:9]([C:15]3[CH:16]=[N:17][N:18]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH:19]=3)[N:10]([S:11]([CH3:14])(=[O:13])=[O:12])[C:4]=2[CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:33][C:34]1[CH:39]=[CH:38][C:37]([F:40])=[CH:36][N:35]=1.O>CC(O)(C)C.CCOC(C)=O.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]>[F:40][C:37]1[CH:38]=[CH:39][C:34]([NH:33][C:2]2[N:7]=[CH:6][C:5]3[CH:8]=[C:9]([C:15]4[CH:16]=[N:17][N:18]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH:19]=4)[N:10]([S:11]([CH3:14])(=[O:13])=[O:12])[C:4]=3[CH:3]=2)=[N:35][CH:36]=1

Participants

8

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 27377012-Amino-5-fluoropyridineHCID 86706273tert-Butyl 4-(6-chloro-1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazole-1-carboxylate

Product 1

HCID 86706304tert-Butyl 4-(6-(5-fluoropyridin-2-ylamino)-1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazole-1-carboxylateYield 36.7%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
80 °C

Procedure

Pd2(dba)3 (9.0 mg, 0.01 mmol) was added to a mixture of tert-butyl 4-(6-chloro-1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazole-1-carboxylate (15) (39 mg, 0.098 mmol), cesium carbonate (128 mg, 0.393 mmol), 2-amino-5-fluoropyridine (22 mg, 0.197 mmol) and di-tBuX-Phos (16.7 mg, 0.039 mmol) in t-BuOH containing water (3%) (1.1 mL). The reaction mixture was heated at 80° C. for 1.5 hr under microwave irradiation. It was then diluted with EtOAc and washed with water. The organic extracts were dried over MgSO4, filtered and concentrated under vacuum. The residue was then purified by prep TLC (DCM/MeOH, 95/5) to afford 17 mg of title compound mixed with some 2-amino-5-fluoropyridine. This mixture was used in the next step without further purification. 1H NMR (500 MHz, CDCl3) 1.70 (s, 9H), 2.97 (s, 3H), 6.72 (d, J=0.9 Hz), 7.37-7.41 (m, 1H), 7.52-7.56 (m, 1H), 7.62 (br s, 1H), 7.95 (m, 1H), 8.17-8.19 (m, 1H), 8.26 (s, 1H), 8.38 (s, 1H), 8.54 (d, J=0.9 Hz, 1H).

Workup

  1. washwashed with water
  2. dry with materialThe organic extracts were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customThe residue was then purified by prep TLC (DCM/MeOH, 95/5)

Sources & evidence

ORD record
ord-aa3dd787c98e483893ff1e00b9bd7b11
Source dataset
uspto-grants-2016_06
Patent number
US09371319B2

Reaction notes

Loading…