Lithium diisopropylamide → HCID 178452223, compound

HRID 1909039Notes

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][N:36]=[C:35]([Br:39])[CH:34]=1.C([N-]C(C)C)(C)C.[Li+]>O1CCCC1>[C:26]([O:25][C:23]([N:20]1[CH2:19][CH2:18][N:17]([C:14]2[N:13]=[C:12]3[NH:8][C:9]([C:32]([C:33]4[CH:38]=[CH:37][N:36]=[C:35]([Br:39])[CH:34]=4)=[O:31])=[N:10][C:11]3=[CH:16][CH:15]=2)[CH2:22][CH2:21]1)=[O:24])([CH3:27])([CH3:28])[CH3:29]

Participants

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 (600 mg, 1.49 mmole), methyl-2-bromo-isonicotinate (321 mg, 1.49 mmole), and tetrahydrofuran (5 ml) was cooled to −78° C. Lithium diisopropylamide (2N, 2.23 ml, 4.46 mmole) was added slowly. Reaction mixture was stirred at −78° C. for 2 hours. Reaction was quenched with water and extracted with EtOAc. EtOAc layer was concentrated and crude product was purified by using silica gel chromatography, eluting with 0% to 40% of EtOAc in CH2Cl2 to afford 4-[2-(2-bromo-pyridine-4-carbonyl)-3H-imidazo[4,5-b]pyridine-5-yl]-piperazine-1-carboxylic acid tert-butyl ester (120 mg, 16.6%). 1H NMR (400 MHz, CD2Cl2) δ 1.58 (s, 9H), 3.59 (m, 4H), 3.74 (m, 4H), 6.89 (d, J=9.03 Hz, 1H), 8.03 (d, J=9.03 Hz, 1H), 8.39 (d, J=5.03 Hz, 1H), 8.61 (d, J=5.02 Hz, 1H), 8.67 (s, 1H). MS(ESI) m/z 488 [M+1].

Workup

customReaction mixture
customReaction
customwas quenched with water
extractionextracted with EtOAc
concentrationEtOAc layer was concentrated
customcrude product was purified
washeluting with 0% to 40% of EtOAc in CH2Cl2

Sources & evidence

ORD record: ord-ef37757ee1bc4921bdbfcb2e5a4b9780
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08598217B2

Reaction notes

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