Lithium diisopropylamide → HCID 178452222, compound

HRID 1909042Notes

Reaction equation

HRID 1909042 reaction equation
C(OC([N:8]1[C:12]2=[N:13][C:14]([N:17]3[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]3)=[CH:15][CH:16]=[C:11]2[N:10]=[CH:9]1)=O)(C)(C)C.C[O:31][C:32](=O)[C:33]1[CH:38]=[CH:37][C:36]([C:39]#[N:40])=[C:35]([C:41]2[C:50]3[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=3)[CH:44]=[N:43][CH:42]=2)[CH:34]=1.C([N-]C(C)C)(C)C.[Li+]>O1CCCC1>[C:26]([O:25][C:23]([N:20]1[CH2:21][CH2:22][N:17]([C:14]2[N:13]=[C:12]3[NH:8][C:9]([C:32](=[O:31])[C:33]4[CH:38]=[CH:37][C:36]([C:39]#[N:40])=[C:35]([C:41]5[C:50]6[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=6)[CH:44]=[N:43][CH:42]=5)[CH:34]=4)=[N:10][C:11]3=[CH:16][CH:15]=2)[CH2:18][CH2:19]1)=[O:24])([CH3:27])([CH3:28])[CH3:29]

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 66599496Methyl 4-cyano-3-(4-isoquinolinyl)benzoateHCID 665995175-(4-Tert-butoxycarbonyl-piperazin-1-yl)-imidazo[4,5-b]pyridine-3-carboxylic acid tert-butyl ester

Product 1

HCID 178452222HCID 178452222, compoundYield 23.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

The mixture of 5-(4-tert-butoxycarbonyl-piperazin-1-yl)-imidazo[4,5-b]pyridine-3-carboxylic acid tert-butyl ester (56 mg, 0.139 mmole), 4-cyano-3-isoquinolin-4-yl-benzoic acid methyl ester (40 mg, 0.139 mmole), and tetrahydrofuran (2 ml) was cooled to −78° C. Lithium diisopropylamide (2N, 0.14 ml, 0.28 mmole) was added slowly. Reaction mixture was stirred at −78° C. for 2 hours and then was quenched with water, extracted with EtOAc. EtOAc layer was concentrated and crude product was purified by using silica gel chromatography, eluting with 20% to 100% EtOAc in heptane to afford 4-[2-(4-cyano-3-isoquinolin-4-yl-benzoyl)-3H-imidazo[4,5-b]pyridine-5-yl]piperazine-1-carboxylic acid tert-butyl ester (18 mg, 23%) as a yellow solid. 1H NMR (400 MHz, CD2Cl2) δ 1.60 (s, 9H), 3.57 (m, 4H), 3.71 (m, 4H), 6.85 (d, J=9.03 Hz, 1H), 7.70 (d, J=7.53 Hz, 1H), 7.78 (m, 2H), 7.95 (d, J=9.03 Hz, 1H), 8.09 (d, J=8.03 Hz, 1H), 8.19 (d, J=8.03 Hz, 1H), 8.62 (s, 1H), 8.84 (s, 1H), 8.89 (d, J=8.53 Hz, 1H), 9.43 (s, 1H), 10.28 (s, 1H). HR-MS m/z 560.2406 (M+1).

Workup

  1. customReaction mixture
  2. customwas quenched with water
  3. extractionextracted with EtOAc
  4. concentrationEtOAc layer was concentrated
  5. customcrude product was purified
  6. washeluting with 20% to 100% EtOAc in heptane

Sources & evidence

ORD record
ord-757efaa27be249cf9b94d504d57efe41
Source dataset
uspto-grants-2013_12
Patent number
US08598217B2

Reaction notes

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