Lithium diisopropylamide → HCID 178482918, compound

HRID 1909033Notes

Reaction equation

C(OC([N:8]1[C:12]2=[N:13][C:14]([N:17]3[CH2:22][CH2:21][CH:20]([N:23]([CH3:25])[CH3:24])[CH2:19][CH2:18]3)=[CH:15][CH:16]=[C:11]2[N:10]=[CH:9]1)=O)(C)(C)C.C[O:27][C:28](=O)[C:29]1[CH:34]=[CH:33][N:32]=[C:31]([Br:35])[CH:30]=1.[Li+].CC([N-]C(C)C)C>>[CH3:25][N:23]([CH3:24])[CH:20]1[CH2:19][CH2:18][N:17]([C:14]2[N:13]=[C:12]3[NH:8][C:9]([C:28]([C:29]4[CH:34]=[CH:33][N:32]=[C:31]([Br:35])[CH:30]=4)=[O:27])=[N:10][C:11]3=[CH:16][CH:15]=2)[CH2:22][CH2:21]1

Participants

Reactant 3

HCID 2724682Lithium diisopropylamide

HCID 38477682-Bromo-isonicotinic acid methyl ester

HCID 66599576HCID 66599576, compound

Product 1

HCID 178482918HCID 178482918, compoundYield 40%

Procedure

Starting with 5-(4-dimethylamino-piperidin-1-yl)-imidazo[4,5-b]pyridin-3-carboxylic acid tert-butyl ester [Example 135, Step 4 (Step 4)] (711 mg, 2.05 mmol) and methyl-2-bromo-isonicotinate (445 mg, 2.05 mmol), the reaction was performed by following General procedure J (LDA metallation) followed by work up method D. Purification by SiO2 chromatography (CH2Cl2/MeOH) gave [5-(4-dimethylamino-piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl]-[2-bromo-pyridin-4-yl]-methanone (350 mg, 40%). 1H NMR (400 MHz, CD3OD) δ 1.43 (m, 2H), 1.93 (m, 2H), 2.26 (s, 6H), 2.47 (m, 1H), 2.87 (m, 2H), 4.53 (m, 2H), 6.95 (d, J=9.54 Hz, 1H), 7.83 (d, J=9.03 Hz, 1H), 8.14 (d, 5.03 Hz, 1H), 8.42 (s, 1H), 8.47 (d, J=5.02 Hz, 1H). MS(ESI) m/z 430 [M+H]+.

Workup

customPurification by SiO2 chromatography (CH2Cl2/MeOH)

Sources & evidence

ORD record: ord-2640691a0b5148e0b7cab8b9dc978205
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08598217B2

Reaction notes

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