1-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → HCID 86728292, compound

HRID 1776913Notes

Reaction equation

HRID 1776913 reaction equation
[F:1][C:2]1[C:3]2[CH:4]=[C:5]3[C:14]4[N:15]=[C:16]([C:19]5[C:20](I)=[CH:21][C:22]6[O:26][C:25]([C:27]7[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=7)=[C:24]([C:34]([NH:36][CH3:37])=[O:35])[C:23]=6[CH:38]=5)[CH:17]=[CH:18][C:13]=4[O:12][CH2:11][N:6]3[C:7]=2[CH:8]=[CH:9][CH:10]=1.[CH3:40][N:41]1[C:45](B2OC(C)(C)C(C)(C)O2)=[CH:44][CH:43]=[N:42]1>CN(C=O)C.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[C:3]2[CH:4]=[C:5]3[C:14]4[N:15]=[C:16]([C:19]5[C:20]([C:45]6[N:41]([CH3:40])[N:42]=[CH:43][CH:44]=6)=[CH:21][C:22]6[O:26][C:25]([C:27]7[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=7)=[C:24]([C:34]([NH:36][CH3:37])=[O:35])[C:23]=6[CH:38]=5)[CH:17]=[CH:18][C:13]=4[O:12][CH2:11][N:6]3[C:7]=2[CH:8]=[CH:9][CH:10]=1

Participants

5

Reactant 2

HCID 49129081-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 71295683HCID 71295683, compound

Product 1

HCID 86728292HCID 86728292, compoundYield 16%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a degassed solution of 5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-6-iodo-N-methylbenzofuran-3-carboxamide (100 mg, 0.16 mmol), 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (100 mg, 0.48 mmol) and K3PO4.3H2O (60 mg, 0.45 mmol) in DMF (2 mL) was added Pd(dppf)Cl2 (20 mg) under N2 protection. The reaction mixture was stirred at 100° C. for 16 hours. The mixture was filtered through a celite pad, and the resulting residue was concentrated to provide crude product. The resulting residue was purified using column chromatography (petroleum ether:EtOAc=1:2) to provide the product of Compound 165 (15 mg, yield: 16%). 1H-NMR (CDCl3, 400 MHz) δ 8.12 (s, 1H), 7.95 (dd, J=8.4, 6.0 Hz, 2H), 7.51 (s, 1H), 7.42 (s, 1H), 7.15 (t, J=8.8 Hz, 5H), 7.02 (d, J=8.0 Hz, 1H), 6.87 (d, J=8.4 Hz, 1H), 6.78 (t, J=8.8 Hz, 1H), 6.24 (s, 1H), 5.96 (s, 1H), 5.88 (s, 2H), 3.38 (s, 3H), 3.00 (d, J=5.2 Hz, 3H). MS (M+H)+: 588.

Workup

  1. filtrationThe mixture was filtered through a celite pad
  2. concentrationthe resulting residue was concentrated
  3. customto provide crude product
  4. customThe resulting residue was purified

Sources & evidence

ORD record
ord-67823ce271f74ef78a522388e1c4e8eb
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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