Triethylamine → 4-methylpiperazine-1-carboxylic acid [3-(1,5,6,7-tetrahydro-1,3-diaza-s-indacen-2-yl)-1-(tetrahydropyran-2-yl)-1H-pyrazol-4-yl]amide

HRID 2064676Notes

Reaction equation

HRID 2064676 reaction equation
NC1C=C(Cl)C(C)=CC=1NC(C1C([N+]([O-])=O)=CNN=1)=O.[NH:21]1[C:32]2[C:24](=[CH:25][C:26]3[CH2:27][CH2:28][CH2:29][C:30]=3[CH:31]=2)[N:23]=[C:22]1[C:33]1[C:37]([NH2:38])=[CH:36][N:35]([CH:39]2[CH2:44][CH2:43][CH2:42][CH2:41][O:40]2)[N:34]=1.C(N(CC)CC)C.[CH3:52][N:53]1[CH2:58][CH2:57][N:56]([C:59](Cl)=[O:60])[CH2:55][CH2:54]1.[Cl-].[Na+].O.C(=O)(O)[O-].[Na+]>O1CCCC1.O>[NH:23]1[C:24]2[C:32](=[CH:31][C:30]3[CH2:29][CH2:28][CH2:27][C:26]=3[CH:25]=2)[N:21]=[C:22]1[C:33]1[C:37]([NH:38][C:59]([N:56]2[CH2:57][CH2:58][N:53]([CH3:52])[CH2:54][CH2:55]2)=[O:60])=[CH:36][N:35]([CH:39]2[CH2:44][CH2:43][CH2:42][CH2:41][O:40]2)[N:34]=1

Participants

9

Reactant 6

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 30169354-Methyl-1-piperazinecarbonyl chlorideHCID 57417360Sodium chloride; waterHCID 1361613043-(1,5,6,7-tetrahydro-1,3-diaza-s-indacen-2-yl)-1-(tetrahydropyran-2-yl)-1H-pyrazol-4-ylamineHCID 178428631HCID 178428631, compound

Product 1

HCID 1357507124-methylpiperazine-1-carboxylic acid [3-(1,5,6,7-tetrahydro-1,3-diaza-s-indacen-2-yl)-1-(tetrahydropyran-2-yl)-1H-pyrazol-4-yl]amide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

By proceeding in a similar manner to Reference Example 48(a) above but (i) treating a solution of 3-(1,5,6,7-tetrahydro-1,3-diaza-s-indacen-2-yl)-1-(tetrahydropyran-2-yl)-1H-pyrazol-4-ylamine [302 mg, Reference Example 49(d)] and triethylamine (0.94 g, 10 eq) in tetrahydrofuran (10 mL) with 4-methylpiperazine-1-carbonyl chloride (930 mg, 4.67 mmol), (ii) stirring the mixture at 45° C. for 4 hours, then at 55° C. for 1 hour, (iii) treating the cooled reaction mixture with aqueous sodium bicarbonate (200 mL) and extracting this mixture three times with ethyl acetate (100 mL), and (iv) evaporating the combined extracts and chromatographing the residue on silica gel (ethyl acetate/gradient 5-20% methanol) there was prepared 4-methylpiperazine-1-carboxylic acid [3-(1,5,6,7-tetrahydro-1,3-diaza-s-indacen-2-yl)-1-(tetrahydropyran-2-yl)-1H-pyrazol-4-yl]amide (189 mg) as a purple solid. LC-MS (Method F): RT=2.28 minutes, 450 (M+H)+.

Workup

  1. waitat 55° C. for 1 hour
  2. extractionextracting this mixture three times with ethyl acetate (100 mL), and (iv)
  3. customevaporating the combined extracts and chromatographing the residue on silica gel (ethyl acetate/gradient 5-20% methanol) there
  4. customwas prepared 4-methylpiperazine-1-carboxylic acid [3-(1,5,6,7-tetrahydro-1,3-diaza-s-indacen-2-yl)-1-(tetrahydropyran-2-yl)-1H-pyrazol-4-yl]amide (189 mg) as a purple solid

Sources & evidence

ORD record
ord-77ca9a2b640d465392275b1fd47802dc
Source dataset
uspto-grants-2012_10
Patent number
US08288425B2

Reaction notes

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