1-(2-Pyridyl)piperazine → HCID 58701857, compound

HRID 269521Notes

Reaction equation

HRID 269521 reaction equation
FC1C(N2CCC(C3C=CC=CN=3)CC2)=CC=C2C=1N(C1C=CC=CC=1C#N)N=C2C.[F:32][C:33]1[C:34](I)=[CH:35][CH:36]=[C:37]2[C:41]=1[N:40]([C:42]1[CH:43]=[C:44]([CH:47]=[CH:48][CH:49]=1)[C:45]#[N:46])[N:39]=[C:38]2[CH3:50].[N:52]1[CH:57]=[CH:56][CH:55]=[CH:54][C:53]=1[N:58]1[CH2:63][CH2:62][NH:61][CH2:60][CH2:59]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.O(C(C)(C)C)[Na]>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:32][C:33]1[C:34]([N:61]2[CH2:62][CH2:63][N:58]([C:53]3[CH:54]=[CH:55][CH:56]=[CH:57][N:52]=3)[CH2:59][CH2:60]2)=[CH:35][CH:36]=[C:37]2[C:41]=1[N:40]([C:42]1[CH:43]=[C:44]([CH:47]=[CH:48][CH:49]=1)[CH2:45][NH2:46])[N:39]=[C:38]2[CH3:50]

Participants

7

Reactant 5

HCID 944591-(2-Pyridyl)piperazineHCID 634876Binap, (A+-)-HCID 69311482HCID 69311482, compoundHCID 86607494HCID 86607494, compoundHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 58701857HCID 58701857, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

3-[7-Fluoro-3-methyl-6-(3′,4′,5′,6′-tetrahydro-2′H-[2,4′]bipyridinyl-1′-yl)-indazol-1-yl-benzonitrile: To a 5 ml round bottom flask equipped with magnetic stirrer, condenser, and argon inlet, 3-(7-fluoro-6-iodo-3-methyl-indazol-1-yl)-benzonitrile (189 mg, 0.5 mmole), 1-pyridin-2-yl piperazine (180 mg, 1.1 mmole), Pd2 (dba)3 (23 mg, 0.025 mmole), BINAP (31 mg, 0.050 mmole), NaO-t-Bu (69 mg, 0.70 mmole) were added. The reaction mixture was purged with argon for 10 minutes. Toluene (0.5 ml) was added. The reaction mixture was heated to reflux for 18 hrs. The reaction was partitioned with EtOAc, and filtered through Celite. The solvent was then removed under vacuum. The desired product (74 mg, 36% yield) was isolated via column chromatography with Hexanes/EtOAc (7/3) as eluent. 1H-NMR (400 MHz, CDCl3): δ 2.62 (s, 3H), 3.33 (t, J=4.93 Hz, 4H), 3.77 (t, J=4.93 Hz, 4H), 6.67-6.71 (m, 1 Hz), 6.74 (d, J=8.79 Hz, 1H), 7.03 (dd, J=8.36 Hz, 6.64 Hz, 1H), 7.44 (d, J=8.57 Hz, 1H), 7.52-7.57 (m, 1H), 7.58-7.65 (m, 2H), 7.86-7.91 (m, 1H), 7.93-7.96 (m, 1H), 8.24-8.26 (m, 1H).

Workup

  1. customThe reaction mixture was purged with argon for 10 minutes
  2. additionToluene (0.5 ml) was added
  3. temperatureThe reaction mixture was heated
  4. temperatureto reflux for 18 hrs
  5. customThe reaction was partitioned with EtOAc
  6. filtrationfiltered through Celite
  7. customThe solvent was then removed under vacuum

Sources & evidence

ORD record
ord-061ade818731498db96a83848738e2cb
Source dataset
uspto-grants-2008_11
Patent number
US07446210B2

Reaction notes

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