Tris(hydroxymethyl)aminomethane → HCID 23030562, compound

HRID 1869588Notes

Reaction equation

HRID 1869588 reaction equation
Cl.[Cl:2][C:3]1[C:4]([N:35]2[CH2:40][CH2:39][CH:38]([C:41](O)=[O:42])[CH2:37][CH2:36]2)=[N:5][CH:6]=[C:7]([C:9](=[O:34])[NH:10][C:11]2[S:12][C:13]([N:22]3[CH2:27][CH2:26][N:25]([CH:28]4[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]4)[CH2:24][CH2:23]3)=[C:14]([C:16]3[S:17][CH:18]=[C:19]([Cl:21])[CH:20]=3)[N:15]=2)[CH:8]=1.[NH:44]1[CH2:49][CH2:48][O:47][CH2:46][CH2:45]1.C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1.[N-]=C=O.C(O)C(N)(CO)CO>C1COCC1>[ClH:2].[Cl:2][C:3]1[C:4]([N:35]2[CH2:40][CH2:39][CH:38]([C:41]([N:44]3[CH2:49][CH2:48][O:47][CH2:46][CH2:45]3)=[O:42])[CH2:37][CH2:36]2)=[N:5][CH:6]=[C:7]([CH:8]=1)[C:9]([NH:10][C:11]1[S:12][C:13]([N:22]2[CH2:23][CH2:24][N:25]([CH:28]3[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]3)[CH2:26][CH2:27]2)=[C:14]([C:16]2[S:17][CH:18]=[C:19]([Cl:21])[CH:20]=2)[N:15]=1)=[O:34]

Participants

8

Reactant 6

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 8083MorpholineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 105034IsocyanateHCID 87588882HCID 87588882, compound

Product 1

HCID 23030562HCID 23030562, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of the compound of Example 16 in 1.8 ml of THF (0.0856 mM), 39 mg of morpholine, 342 mg of PS-DCC (1.35 mmol/g), and 0.2 ml of a solution of HOBt in THF (0.77 mM) were added, and the mixture was stirred at room temperature overnight. To the reaction solution, 2 ml of THF, 370 mg of PS-isocyanate (1.25 mmol/g), and 205 mg of PS-trisamine (3.75 mmol/g) were added, and the mixture was stirred at room temperature for 1 hour. The reaction solution was filtered, and the obtained residue was purified by silica gel column chromatography (chloroform-MeOH=99:1˜97:3) and the obtained compound was dissolved in 2 ml of EtOAc. And, 1 ml of 4M HCl-EtOAc was added thereto at room temperature, and the mixture was stirred for 15 minutes. The thus-precipitated solid was collected by filtration to obtain 84 mg of 5-chloro-N-[4-(4-chlorothiophen-2-yl)-5-(4-cyclohexylpiperazin-1-yl)thiazol-2-yl]-6-[4-(morpholinocarbonyl)piperidino]nicotinamide hydrochloride.

Workup

  1. stirringthe mixture was stirred at room temperature for 1 hour
  2. filtrationThe reaction solution was filtered
  3. customthe obtained residue was purified by silica gel column chromatography (chloroform-MeOH=99:1˜97:3)
  4. dissolutionthe obtained compound was dissolved in 2 ml of EtOAc
  5. additionAnd, 1 ml of 4M HCl-EtOAc was added
  6. stirringat room temperature, and the mixture was stirred for 15 minutes
  7. filtrationThe thus-precipitated solid was collected by filtration

Sources & evidence

ORD record
ord-ef74a21df85040db8acc8dfc1e13b82c
Source dataset
uspto-grants-2009_12
Patent number
US07638536B2

Reaction notes

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