Ethyl Acetate → HCID 178433731, compound

HRID 1909060Notes

Reaction equation

HRID 1909060 reaction equation
CN(C[N:5]1[C:9]2=[N:10][C:11]([N:14]3[CH2:19][CH2:18][CH:17]([N:20]([CH3:22])[CH3:21])[CH2:16][CH2:15]3)=[CH:12][CH:13]=[C:8]2[N:7]=[CH:6]1)C.C(NC(C)C)(C)C.[Li].C[O:32][C:33](=O)[C:34]1[CH:39]=[CH:38][C:37]([C:40]#[N:41])=[C:36]([C:42]2[C:46]([CH3:47])=[N:45][N:44]3[CH2:48][CH2:49][CH2:50][C:43]=23)[CH:35]=1.CCOC(C)=O>C1COCC1>[CH3:22][N:20]([CH3:21])[CH:17]1[CH2:16][CH2:15][N:14]([C:11]2[N:10]=[C:9]3[NH:5][C:6]([C:33]([C:34]4[CH:39]=[CH:38][C:37]([C:40]#[N:41])=[C:36]([C:42]5[C:46]([CH3:47])=[N:45][N:44]6[CH2:48][CH2:49][CH2:50][C:43]=56)[CH:35]=4)=[O:32])=[N:7][C:8]3=[CH:13][CH:12]=2)[CH2:19][CH2:18]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 45051747Lithium diisopropylamineHCID 66599667[1-(3-dimethylaminomethyl-3H-imidazo[4,5-b]pyridin-5-yl)-piperidin-4-yl]-dimethyl-amineHCID 66599721HCID 66599721, compound

Product 1

HCID 178433731HCID 178433731, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a solution of [1-(3-dimethylaminomethyl-3H-imidazo[4,5-b]pyridin-5-yl)-piperidin-4-yl]-dimethyl-amine (0.36 g, 1.2 mmol) in THF (5 mL) at −78° C. under N2 was added dropwise a freshly prepared solution of lithium diisopropylamine (1M, 1.5 mL, 1.5 mmol) in THF. After 10 m at −78° C. a solution of 4-cyano-3-(2-methyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-benzoic acid methyl ester (0.28 g, 1.0 mmol) in THF (5 mL) was added. The reaction mixture was stirred at −78° C. under N2 for 15 m before quenching with a 1:1 solution of acetic acid and water (2 mL). After warming to room temperature the quenched reaction was diluted several fold EtOAc and washed with dilute NH4OH followed by brine. The organic layer was dried over Na2SO4, filtered and concentrated. After purifying the crude product by reverse phase HPLC, the product was neutralized with aqueous Na2CO3 yielding the desired product as a orange-colored solid (50 mg, 0.10 mmol). 1H NMR (400 MHz, DMSO-d6) □ ppm 1.32-1.44 (m, J=12.00, 11.81, 11.81, 3.79 Hz, 2H) 1.85 (d, J=10.61 Hz, 2H) 2.20 (s, 6H) 2.25 (s, 3H) 2.33-2.46 (m, 1H) 2.53-2.63 (m, 2H) 2.89-3.02 (m, 4H) 4.43 (d, J=13.14 Hz, 2H) 7.04 (d, J=9.09 Hz, 1H) 7.95 (d, J=9.09 Hz, 1H) 8.10 (d, J=8.08 Hz, 1H) 8.36 (d, J=7.58 Hz, 1H) 8.52 (s, 1H); MS m/z 495.5 (M+H)+.

Workup

  1. custombefore quenching with a 1:1 solution of acetic acid and water (2 mL)
  2. temperatureAfter warming to room temperature
  3. customthe quenched reaction
  4. washwashed with dilute NH4OH
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customAfter purifying the crude product by reverse phase HPLC

Sources & evidence

ORD record
ord-d2e0f81039e14b6b8378f55b6c401c1a
Source dataset
uspto-grants-2013_12
Patent number
US08598217B2

Reaction notes

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