Dichloromethane → Methyl 3-(1-(4-fluorophenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)isonicotinate

HRID 1186800Notes

Reaction equation

HRID 1186800 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16](B(O)O)=[C:11]3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[CH3:20][O:21][C:22]([C:24]1[CH:29]=[CH:28][N:27]=[CH:26][C:25]=1Br)=[O:23].C(=O)([O-])[O-].[K+].[K+].C(Cl)Cl>CN1C(=O)CCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([C:29]4[CH:28]=[N:27][CH:26]=[CH:25][C:24]=4[C:22]([O:21][CH3:20])=[O:23])=[C:11]3[CH:10]=[N:9]2)=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 2762700Methyl 3-bromoisonicotinateHCID 666684341-(4-fluorophenyl)-1H-pyrazolo[3,4-b]pyridin-4-ylboronic acid

Product 1

HCID 56603075Methyl 3-(1-(4-fluorophenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)isonicotinateYield 21.2%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Example 12 was prepared according to the general procedure of Example 1, except that the reaction mixture was heated at 105° C. for 1 h in a mixture of NMP (1.0 mL) and water (50 μL) and using the following materials: Intermediate 5A (49.4 mg, 0.192 mmol), 3-bromopyridine-4-carboxylic acid methyl ester (0.035 mL, 0.268 mmol), potassium carbonate (93 mg, 0.671 mmol), and PdCl2(dppf).CH2Cl2 (9 mg, 0.012 mmol). Example 12 was isolated as a tan solid (14.2 mg, 19.8%). Purification was done by preparative HPLC (Condition A) using a Phenomenex Luna Axia 30×100 mm S10 column from 30% Solvent B to 100% Solvent B over 12 min, ret. T=10.7 min. LC/MS (Condition B): ret. T=3.6 min, (M+H)+ 349.14. Analytical HPLC: (Condition A): >90%, ret. T=22.18 min, (Condition B): >95%, ret. T=22.85 min, (Condition C): >95%, ret. T=17.14 min, (Condition D): >95%, ret. T=13.96 min.

Workup

  1. customExample 12 was prepared

Sources & evidence

ORD record
ord-10b134c2251440d4896b60bdb8945f6f
Source dataset
uspto-grants-2014_03
Patent number
US08673922B2

Reaction notes

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