Piperazine → HCID 178458675, compound

HRID 518734Notes

Reaction equation

HRID 518734 reaction equation
[F:1][C:2]1[CH:39]=[CH:38][C:5]([C:6](/[N:8]=[C:9]2\[NH:10][C:11]3[CH:26]=[CH:25][C:24]([CH2:27][N:28]4[CH2:33][CH2:32][CH:31]([C:34]([OH:37])([CH3:36])[CH3:35])[CH2:30][CH2:29]4)=[CH:23][C:12]=3[N:13]\2[C@@H:14]2[CH2:19][CH2:18][C@H:17]([C:20]([OH:22])=O)[CH2:16][CH2:15]2)=[O:7])=[CH:4][CH:3]=1.CN(C(ON1N=[N:55][C:50]2C=[CH:52][CH:53]=[N:54][C:49]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.N1CCNCC1>CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:6](/[N:8]=[C:9]2\[NH:10][C:11]3[CH:26]=[CH:25][C:24]([CH2:27][N:28]4[CH2:29][CH2:30][CH:31]([C:34]([OH:37])([CH3:35])[CH3:36])[CH2:32][CH2:33]4)=[CH:23][C:12]=3[N:13]\2[C@H:14]2[CH2:19][CH2:18][C@@H:17]([C:20]([N:54]3[CH2:49][CH2:50][NH:55][CH2:52][CH2:53]3)=[O:22])[CH2:16][CH2:15]2)=[O:7])=[CH:38][CH:39]=1

Participants

6

Reactant 4

HCID 4837PiperazineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178458676HCID 178458676, compound

Product 1

HCID 178458675HCID 178458675, compoundYield 59.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of cis-4-((E)-2-(4-fluorobenzoylimino)-6-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)-2,3-dihydro-1H-benzo[d]imidazol-1-yl)cyclohexanecarboxylic acid (100 mg, 0.186 mmol) in DMF (3 mL) was added HATU (74.4 mg, 0.196 mmol) and DIPEA (0.036 mL, 0.205 mmol). The suspension was stirred for 15 minutes at RT. A solution of piperazine (161 mg, 1.863 mmol) in DMF (1 mL) was added, and the reaction was stirred at RT overnight. The reaction mixture was partitioned between water and EtOAc. The organic layer was concentrated and the residue purified by HPLC (15-90% ACN/0.1% TFA). The product fractions were combined, neutralized with saturated aqueous NaHCO3, and extracted with EtOAc (×2). The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated to provide (E)-4-fluoro-N-(6-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)-1-(cis-4-(piperazine-1-carbonyl)cyclohexyl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide as a white powder (67 mg, 59.5% yield). MS, m/z (C34H45FN6O3): calcd, 604.3. found, 605.1 [M+H].

Workup

  1. stirringthe reaction was stirred at RT overnight
  2. customThe reaction mixture was partitioned between water and EtOAc
  3. concentrationThe organic layer was concentrated
  4. customthe residue purified by HPLC (15-90% ACN/0.1% TFA)
  5. extractionextracted with EtOAc (×2)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-b5594ada08f14df7a630d4cd6c9d12a0
Source dataset
uspto-grants-2015_08
Patent number
US09115127B2

Reaction notes

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