1,2-Dichloroethane → HCID 178426404, compound

HRID 526648Notes

Reaction equation

HRID 526648 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[N:11][N:12]([C:15]3[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][N:16]=3)[C:13]=2[OH:14])=[C:5]([CH3:24])[CH:4]=1)#[N:2].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[CH2:48]1[NH:53][CH2:52][CH2:51][N:50]2[CH2:54][CH2:55][CH2:56][CH:49]12>CN(C=O)C>[OH:14][C:13]1[N:12]([C:15]2[CH:23]=[CH:22][C:18]([C:19]([N:53]3[CH2:52][CH2:51][N:50]4[CH2:54][CH2:55][CH2:56][CH:49]4[CH2:48]3)=[O:21])=[CH:17][N:16]=2)[N:11]=[CH:10][C:9]=1[C:6]1[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][C:5]=1[CH3:24]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 558578Octahydropyrrolo(1,2-a)pyrazineHCID 178426451HCID 178426451, compound

Product 1

HCID 178426404HCID 178426404, compoundYield 38.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Combined 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid (500 mg, 1.561 mmol), EDC (449 mg, 2.342 mmol) and HOBT (316 mg, 2.342 mmol) in DMF (3122 μl) and treated with DIPEA (818 μl, 4.68 mmol). Octahydropyrrolo[1,2-a]pyrazine (296 mg, 2.342 mmol) was then added. The reaction was allowed to stir for 8 hours and filtered and the filtrate was purified by preparative HPLC (15-40% ACN/water under basic conditions) to give a solid which was recrystallized from MeOH, filtered, and dried in vacuum to give the title compound (286 mg, 0.603 mmol, 38.6%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.34 (br. s., 1H) 1.72 (br. s., 3H) 2.12 (br. s., 1H) 2.23 (d, J=7.07 Hz, 2H) 2.42 (s, 3H) 2.51-2.53 (m, 1H) 3.06 (t, J=8.08 Hz, 3H) 3.72 (br. s., 1H) 4.44-4.56 (m, 1H) 7.63 (dd, J=8.08, 1.77 Hz, 1H) 7.69 (d, J=1.26 Hz, 1H) 7.84 (d, J=8.08 Hz, 1H) 8.04 (dd, J=8.59, 2.27 Hz, 1H) 8.09 (s, 1H) 8.40 (d, J=7.58 Hz, 1H) 8.52 (d, J=2.27 Hz, 1H); ESI-MS m/z (M+H)+ calc'd for C24H24N6O2, 429.20. found 429.3.

Workup

  1. filtrationfiltered
  2. customthe filtrate was purified by preparative HPLC (15-40% ACN/water under basic conditions)
  3. customto give a solid which
  4. customwas recrystallized from MeOH
  5. filtrationfiltered
  6. customdried in vacuum

Sources & evidence

ORD record
ord-26ba9cc30f9c425dbf478c855f964543
Source dataset
uspto-grants-2016_05
Patent number
US09345713B2

Reaction notes

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