Diisopropylethylamine → HCID 178522371, compound

HRID 2274383Notes

Reaction equation

HRID 2274383 reaction equation
[N:1]1([C:7](Cl)=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)C(C)C)(C)C.[F:19][C:20]1[C:40]([N:41]2[CH2:46][CH2:45][O:44][CH2:43][CH2:42]2)=[CH:39][C:23]2[NH:24][C:25]([C:27]3[C:31]([NH2:32])=[CH:30][N:29]([CH:33]4[CH2:38][CH2:37][CH2:36][CH2:35][O:34]4)[N:28]=3)=[N:26][C:22]=2[CH:21]=1>C1COCC1>[F:19][C:20]1[C:40]([N:41]2[CH2:42][CH2:43][O:44][CH2:45][CH2:46]2)=[CH:39][C:23]2[NH:24][C:25]([C:27]3[C:31]([NH:32][C:7]([N:1]4[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]4)=[O:8])=[CH:30][N:29]([CH:33]4[CH2:38][CH2:37][CH2:36][CH2:35][O:34]4)[N:28]=3)=[N:26][C:22]=2[CH:21]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 2420851-Piperidinecarbonyl chlorideHCID 178507992HCID 178507992, compound

Product 1

HCID 178522371HCID 178522371, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

10 mL of piperidinecarbonyl chloride and 13.55 mL of N,N-diisopropylethylamine are added to a solution of 10 g of 3-(5-fluoro-6-morpholin-4-yl-1H-benzimidazol-2-yl)-1-(tetrahydropyran-2-yl)-1H-pyrazol-4-ylamine in 200 mL of THF. The reaction mixture is refluxed for 3 hours and then left stirring at ambient temperature for 48 hours. After concentration of the medium vacuum in a rotary evaporator, the reaction crude is purified by flash chromatography on 1200 g of 40-63 μM silica, elution being carried out with a 90:10 mixture of dichloromethane/acetone. 10.4 g of piperidine-1-carboxylic acid [3-(5-fluoro-6-morpholin-4-yl-1H-benzimidazol-2-yl)-1-(tetrahydropyran-2-yl)-1H-pyrazol-4-yl]amide are isolated. 1H NMR (300 MHz, (CD3)2S, δ in ppm): 1.50-1.79 (m: 10H); 1.91-2.04 (m: 2H); 3.00 (m: 4H); 3.50 (m: 4H); 3.66 (m: 1H); 3.77 (m: 4H); 3.96 (broad d J=11 Hz: 1H); 5.46 (dd, J=10 and 2 Hz: 1H); 7.10 (very broad s: 1H); 7.40 (very broad s: 1H); 8.13 (s: 1H); 9.96 (broad s: 1H); 13.00 (very broad s: 1H).

Workup

  1. temperatureThe reaction mixture is refluxed for 3 hours
  2. waitleft
  3. customAfter concentration of the medium vacuum in a rotary evaporator
  4. customthe reaction crude
  5. customis purified by flash chromatography on 1200 g of 40-63 μM silica, elution
  6. additionbeing carried out with a 90:10 mixture of dichloromethane/acetone

Sources & evidence

ORD record
ord-1b9e88d8638f472b96faaf8e2bcea2d4
Source dataset
uspto-grants-2015_09
Patent number
US09126969B2

Reaction notes

Loading…