1,2-Dichloroethane → HCID 66604375, compound

HRID 2410692Notes

Reaction equation

HRID 2410692 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([C:8]([OH:10])=O)[CH2:4][CH2:3]1.CCN(C(C)C)C(C)C.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[NH2:34][C:35]1[CH:47]=[C:46]2[C:38]([C:39]3[CH:40]=[C:41]([C:51]4[CH:56]=[CH:55][CH:54]=[C:53]([O:57][CH3:58])[CH:52]=4)[CH:42]=[C:43]([C:48]([NH2:50])=[O:49])[C:44]=3[NH:45]2)=[CH:37][CH:36]=1>CN(C=O)C.CO>[CH3:58][O:57][C:53]1[CH:52]=[C:51]([C:41]2[CH:42]=[C:43]([C:48]([NH2:50])=[O:49])[C:44]3[NH:45][C:46]4[C:38]([C:39]=3[CH:40]=2)=[CH:37][CH:36]=[C:35]([NH:34][C:8]([CH:5]2[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]2)=[O:10])[CH:47]=4)[CH:56]=[CH:55][CH:54]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27369391-Methylpiperidine-4-carboxylic acidHCID 66604487HCID 66604487, compound

Product 1

HCID 66604375HCID 66604375, compoundYield 69%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-methylpiperidine-4-carboxylic acid (25.9 mg, 0.181 mmol) in DMF (0.5 mL), were successively added N,N′-diisopropylethylamine (0.053 mL, 0.302 mmol), EDC (23.14 mg, 0.121 mmol) and HOBt (18.49 mg, 0.121 mmol). After stirring at room temperature for 5 min, 7-amino-3-(3-methoxyphenyl)-9H-carbazole-1-carboxamide (20 mg, 0.060 mmol, Example 138) was added. After stirring for 16 h, the reaction was diluted with MeOH, and the product was isolated by preparative HPLC (100×30 mm Luna C18 column, flow rate 42 ml permin, gradient elution starting with A:B=90:10 and ending with A:B=30:70 [A=10 mM NH4OAc in 5% aqueous acetonitrile; B=10 mM NH4OAc in 95% aqueous acetonitrile] over 20 min). The HPLC fractions that contained the product were applied onto a PHENOMENEX® Strata-X-C 33 um cation mixed-mode polymer cartridge. This was washed with methanol and product was eluted with 2 N solution of ammonia in methanol. Removal of the solvents gave 18.9 mg of 3-(3-methoxyphenyl)-7-(1-methylpiperidine-4-carboxamido)-9H-carbazole-1-carboxamide as a white solid. MS (ESI) m/z 457.2 (M+H). 1H NMR (MeOD) δ ppm 8.43 (1H, s), 8.13 (1H, d, J=1.22 Hz), 8.08 (1H, d, J=8.55 Hz), 8.04 (1H, s), 7.30 -7.43 (3H, m), 7.27 (1H, dd, J=8.39, 1.68 Hz), 6.92 (1H, dd, J=5.49, 2.14 Hz), 3.90 (3H, s), 3.00 (2H, d, J=11.60 Hz), 2.38-2.51 (1H, m), 2.33 (3H, s), 2.06-2.20 (2H, m), 1.85-2.04 (4H, m).

Workup

  1. stirringAfter stirring for 16 h
  2. customthe product was isolated by preparative HPLC (
  3. wash100×30 mm Luna C18 column, flow rate 42 ml permin, gradient elution
  4. waitB=10 mM NH4OAc in 95% aqueous acetonitrile] over 20 min)
  5. additionmixed-mode polymer cartridge
  6. washThis was washed with methanol and product
  7. washwas eluted with 2 N solution of ammonia in methanol
  8. customRemoval of the solvents

Sources & evidence

ORD record
ord-d85b7b3a1e6248e9aa9b61ff457c3a4e
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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