Triethylamine → HCID 178462796, compound

HRID 1645349Notes

Reaction equation

HRID 1645349 reaction equation
[CH2:1]([O:8][C:9]([C@H:11]1[CH2:16][CH2:15][C@H:14]([C:17]([OH:19])=O)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[N:26]1([C:32]2[N:37]=[CH:36][C:35]([NH:38][C:39]([C:41]3[N:42]([CH2:52][CH3:53])[C:43]4[C:48]([CH:49]=3)=[C:47]([O:50][CH3:51])[CH:46]=[CH:45][CH:44]=4)=[O:40])=[CH:34][CH:33]=2)[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.C(N(CC)CC)C>C(Cl)Cl.CN(C=O)C>[CH2:1]([O:8][C:9]([C@H:11]1[CH2:12][CH2:13][C@H:14]([C:17]([N:29]2[CH2:30][CH2:31][N:26]([C:32]3[CH:33]=[CH:34][C:35]([NH:38][C:39]([C:41]4[N:42]([CH2:52][CH3:53])[C:43]5[C:48]([CH:49]=4)=[C:47]([O:50][CH3:51])[CH:46]=[CH:45][CH:44]=5)=[O:40])=[CH:36][N:37]=3)[CH2:27][CH2:28]2)=[O:19])[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 593651261-ethyl-4-methoxy-1H-indole-2-carboxylic acid (6-piperazin-1-yl-pyridin-3-yl)-amideHCID 178525735HCID 178525735, compound

Product 1

HCID 178462796HCID 178462796, compoundYield 37%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of trans-cyclohexane-1,4-dicarboxylic acid mono-benzyl ester (50 mg, 0.16 mmol), CH2Cl2 (5 mL), and a catalytic amount of DMF was stirred under Ar, and oxalyl chloride (2M in dichloromethane, 200 μL, 0.4 mmol) was dripped into the mixture over 5 min. The mixture was stirred at room temperature and after 1.0 hr the reaction was concentrated to dryness. Benzene was added and the solution was evaporated to dryness again. The white-yellow solid was re-dissolved in 5 mL of CH2Cl2 and dripped, under Ar, into a solution of 1-ethyl-4-methoxy-1H-indole-2-carboxylic acid (6-piperazin-1-yl-pyridin-3-yl)-amide (60.0 mg, 0.16 mmol), triethylamine (0.41 mg, 0.2 mmol) in 5 mL of CH2Cl2. The reaction was stirred at room temperature for 0.5 hr then concentrated and the residue was taken up in 50 mL of EtOAc and washed with 50 mL of saturated ammonium chloride, brine and dried with anhydrous sodium sulfate. The solvent was removed, and the crude product was purified by flash chromatography (hexanes:EtOAc), to afford the product trans-4-(4-{5-[(1-ethyl-4-methoxy-1H-indole-2-carbonyl)-amino]-pyridin-2-yl}-piperazine-1-carbonyl)-cyclohexanecarboxylic acid benzyl ester (35 mg, 37% yield) as a white solid. LCMS for C36H41N5O5 calcd. (m/e) 623, observed 624 (M+H).

Workup

  1. concentrationwas concentrated to dryness
  2. additionBenzene was added
  3. customthe solution was evaporated to dryness again
  4. dissolutionThe white-yellow solid was re-dissolved in 5 mL of CH2Cl2
  5. stirringThe reaction was stirred at room temperature for 0.5 hr
  6. concentrationthen concentrated
  7. washwashed with 50 mL of saturated ammonium chloride, brine
  8. dry with materialdried with anhydrous sodium sulfate
  9. customThe solvent was removed
  10. customthe crude product was purified by flash chromatography (hexanes:EtOAc)

Sources & evidence

ORD record
ord-c7303844091149a6a7d1b79234c0d173
Source dataset
uspto-grants-2012_02
Patent number
US08124766B2

Reaction notes

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