1-Hydroxybenzotriazole → HCID 24966090, compound

HRID 420129Notes

Reaction equation

HRID 420129 reaction equation
C([O:5][C:6]([C:8]1[C:16]2[C:11](=[CH:12][C:13]([C:20](O)=[O:21])=[CH:14][C:15]=2[O:17][CH2:18][CH3:19])[N:10]([CH:23]2[CH2:25][CH2:24]2)[CH:9]=1)=[O:7])(C)(C)C.Cl.[NH:27]1[CH:31]=[C:30]([C:32]2[CH:33]=[C:34]3[C:44](=[CH:45][CH:46]=2)[O:43][C:37]2([CH2:42][CH2:41][NH:40][CH2:39][CH2:38]2)[CH2:36][C:35]3=[O:47])[CH:29]=[N:28]1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.C(OCC)(=O)C.C(N(CC)CC)C>[CH:23]1([N:10]2[C:11]3[C:16](=[C:15]([O:17][CH2:18][CH3:19])[CH:14]=[C:13]([C:20]([N:40]4[CH2:41][CH2:42][C:37]5([CH2:36][C:35](=[O:47])[C:34]6[C:44](=[CH:45][CH:46]=[C:32]([C:30]7[CH:31]=[N:27][NH:28][CH:29]=7)[CH:33]=6)[O:43]5)[CH2:38][CH2:39]4)=[O:21])[CH:12]=3)[C:8]([C:6]([OH:7])=[O:5])=[CH:9]2)[CH2:24][CH2:25]1

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66649443HCID 66649443, compoundHCID 66649461HCID 66649461, compound

Product 1

HCID 24966090HCID 24966090, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

Triethylamine (0.21 mL) was added to a solution of 3-(tert-butoxycarbonyl)-1-cyclopropyl-4-ethoxy-1H-indole-6-carboxylic acid (177 mg), 6-(1H-pyrazol-4-yl)spiro[chroman-2,4′-piperidin]-4-one hydrochloride (156 mg), WSC hydrochloride (106 mg) and HOBT (85 mg) in DMF (4 mL) and the mixture was stirred at 90° C. for 1 hour. After cooling to room temperature, the mixture was diluted with ethyl acetate, then washed with water, 1N hydrochloric acid solution, aqueous saturated sodium bicarbonate and saturated saline in this order, and dried over sodium sulfate. The solution was filtered, concentrated, and purified through silica gel column chromatography (chloroform/methanol) to give the methyl ester of the title compound as a colorless amorphous substance. TFA (3 ml) was added to the solution of this ester in chloroform (10 ml) at room temperature and stirred for 3 h. The solvent was evaporated and the residue was crystallized from a mixed solvent of methanol and ether to give title compound as a colorless solid. 1H-NMR (400 MHz, DMSO-d6) δ: 8.03 (2H, s), 7.94 (1H, s), 7.87 (1H, d, J=2.4 Hz), 7.83 (1H, dd, J=8.5, 2.4 Hz), 7.33 (1H, d, J=1.0 Hz), 7.10 (1H, d, J=8.5 Hz), 6.79 (1H, d, J=1.0 Hz), 4.31-4.19 (1H, br m), 4.21 (2H, q, J=7.0 Hz), 3.85-3.21 (4H, br m), 2.89 (2H, s), 2.11-1.70 (4H, br m), 1.39 (3H, t, J=7.0 Hz), 1.10-1.00 (4H, m); MS [M+H]+=555.

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed with water, 1N hydrochloric acid solution, aqueous saturated sodium bicarbonate and saturated saline in this order
  3. dry with materialdried over sodium sulfate
  4. filtrationThe solution was filtered
  5. concentrationconcentrated
  6. custompurified through silica gel column chromatography (chloroform/methanol)

Sources & evidence

ORD record
ord-aea1c4f35a524eefb3e90fe18161761f
Source dataset
uspto-grants-2012_01
Patent number
US08093389B2

Reaction notes

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