HCID 69938122, compound → HCID 71256097, compound

HRID 388438Notes

Reaction equation

HRID 388438 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C:12]3[CH:13]=[C:14]([N:18]([CH3:30])[C:19](=[O:29])/[CH:20]=[CH:21]/[CH2:22][N:23]([CH:25]4[CH2:28][CH2:27][CH2:26]4)[CH3:24])[CH:15]=[CH:16][CH:17]=3)[N:9]=[C:10](I)[C:3]=12.[CH3:31][O:32][C:33]1[CH:34]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:36]=[CH:37][C:38]=1[CH3:39]>CN(C=O)C.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]>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C:12]3[CH:13]=[C:14]([N:18]([CH3:30])[C:19](=[O:29])/[CH:20]=[CH:21]/[CH2:22][N:23]([CH:25]4[CH2:28][CH2:27][CH2:26]4)[CH3:24])[CH:15]=[CH:16][CH:17]=3)[N:9]=[C:10]([C:35]3[CH:36]=[CH:37][C:38]([CH3:39])=[C:33]([O:32][CH3:31])[CH:34]=3)[C:3]=12

Participants

5

Reactant 2

HCID 69938122HCID 69938122, compoundHCID 71256152HCID 71256152, compound

Product 1

HCID 71256097HCID 71256097, compoundYield 14.2%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of (E)-N-(3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)phenyl)-4-(cyclobutyl(methyl)amino)-N-methylbut-2-enamide (52) (222 mg, 0.4 mmol) and 2-(3-methoxy-4-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (119 mg, 0.48 mmol) in DMF/H2O (4 mL/1 mL) were added Pd(dppf)Cl2 (16 mg, 0.02 mmol) and K3PO4.3H2O (320 mg, 1.2 mmol). The resulting mixture was purged with N2 (3×) and stirred at 80° C. overnight. Solvents were removed in vacuo. The residue was pre-purified by flash chromatography (silica gel, 0 to 10% MeOH in DCM with 0.3% TEA) followed by a prep HPLC to provide (E)-N-(3-(4-amino-3-(3-methoxy-4-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)phenyl)-4-(cyclobutyl(methyl)amino)-N-methylbut-2-enamide (53) (29 mg, 14%) as a white solid. LC-MS (ESI): m/z (M+1) 512.3. 1H NMR (400 MHz, DMSO) δ 8.39 (s, 1H), 8.29 (d, J=9.4 Hz, 1H), 8.19 (t, J=2.0 Hz, 1H), 7.65 (t, J=8.1 Hz, 1H), 7.36 (d, J=7.6 Hz, 1H), 7.32-7.22 (m, 3H), 6.72-6.61 (m, 1H), 5.99 (d, J=13.0 Hz, 1H), 3.89 (s, 3H), 2.98-2.78 (m, 2H), 2.77-2.62 (m, 1H), 2.25 (s, 3H), 1.87 (s, 3H), 1.83-1.71 (m, 2H), 1.71-1.54 (m, 2H), 1.50-1.32 (m, 2H).

Workup

  1. customThe resulting mixture was purged with N2 (3×)
  2. customSolvents were removed in vacuo
  3. customThe residue was pre-purified by flash chromatography (silica gel, 0 to 10% MeOH in DCM with 0.3% TEA)

Sources & evidence

ORD record
ord-343bd1d27e524ba58ad9be86a52347d0
Source dataset
uspto-grants-2013_02
Patent number
US08377946B1

Reaction notes

Loading…