Diisopropylethylamine → HCID 178452210, compound

HRID 2274436Notes

Reaction equation

HRID 2274436 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.[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][N:29]([C:32]2[C:52]([F:53])=[CH:51][C:35]3[N:36]=[C:37]([C:39]4[C:43]([NH2:44])=[CH:42][N:41]([CH:45]5[CH2:50][CH2:49][CH2:48][CH2:47][O:46]5)[N:40]=4)[NH:38][C:34]=3[CH:33]=2)[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20].C(=O)(O)[O-].[Na+]>C1COCC1>[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][N:29]([C:32]2[C:52]([F:53])=[CH:51][C:35]3[N:36]=[C:37]([C:39]4[C:43]([NH:44][C:7]([N:1]5[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]5)=[O:8])=[CH:42][N:41]([CH:45]5[CH2:50][CH2:49][CH2:48][CH2:47][O:46]5)[N:40]=4)[NH:38][C:34]=3[CH:33]=2)[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:20])[CH3:21]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2420851-Piperidinecarbonyl chlorideHCID 516892Sodium BicarbonateHCID 178452211HCID 178452211, compound

Product 1

HCID 178452210HCID 178452210, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

1.2 mL of 1-piperidinecarbonyl chloride and 1.7 mL of N,N-diisopropylethylamine are added to a solution of 480 mg of 4-{2-[4-amino-1-(tetrahydropyran-2-yl)-1H-pyrazol-3-yl]-6-fluoro-3H-benzimidazol-5-yl}piperazine-1-carboxylic acid tert-butyl ester in 10 mL of THF. The reaction mixture is heated at 80° C. for 16 hours. The reaction medium is cooled to ambient temperature and 20 mL of a saturated solution of sodium bicarbonate are added. The aqueous phases are extracted with 3 times 10 mL of EtOAc. The organic phases are dried over MgSO4, filtered and concentrated under vacuum in a rotary evaporator. The reaction crude is purified by flash chromatography, elution being carried out with a mixture of cyclohexane/ethyl acetate. 350 mg of 4-{6-fluoro-2-[4-[(piperidine-1-carbonyl)amino]-1-(tetrahydropyran-2-yl)-1H-pyrazol-3-yl]-3H-benzimidazol-5-yl}piperazine-1-carboxylic acid tert-butyl ester are obtained in the form of a brown foam. 1H NMR (400 MHz, DMSO-d6, δ in ppm): from 1.37 to 2.22 (m, 12H); 1.42 (s, 9H); 3.04 (m, 4H); 3.44 (m, 4H); 3.53 (m, 4H); 3.67 (m, 1H); 3.96 (m, 1H); 5.52 (dd, J=2.0 and 10.0 Hz, 1H); 7.29 (d, J=7.5 Hz, 1H); 7.56 (d, J=11.5 Hz, 1H); 8.15 (s, 1H). ES mass spectrum: m/z=597 MH+ (base peak).

Workup

  1. temperatureThe reaction medium is cooled to ambient temperature
  2. extractionThe aqueous phases are extracted with 3 times 10 mL of EtOAc
  3. dry with materialThe organic phases are dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum in a rotary evaporator
  6. customThe reaction crude
  7. customis purified by flash chromatography, elution
  8. additionbeing carried out with a mixture of cyclohexane/ethyl acetate

Sources & evidence

ORD record
ord-6aaa48bc96034410b2c0a71e44ff21fb
Source dataset
uspto-grants-2015_09
Patent number
US09126969B2

Reaction notes

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