Tetrahydrofuran → HCID 178434017, compound
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.COC(=O)[C:29]1[CH:34]=[CH:33]N=C[C:30]=1[C:35]1[C:36]([CH3:42])=[N:37][N:38]([CH3:41])[C:39]=1[CH3:40].[Li+].CC([N-:48][CH:49](C)C)C.[O:52]1CCC[CH2:53]1>>[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:53]([C:34]4[CH:33]=[CH:49][N:48]=[C:30]([C:35]5[C:36]([CH3:42])=[N:37][N:38]([CH3:41])[C:39]=5[CH3:40])[CH:29]=4)=[O:52])=[N:10][C:11]3=[CH:16][CH:15]=2)[CH2:22][CH2:21]1Participants
Conditions
- Temperature
- -78 °C
Procedure
A mixture of 5-(4-dimethylamino-piperidin-1-yl)-imidazo[4,5-b]pyridin-3-carboxylic acid tert-butyl ester (Step 1) (50 mg, 0.145 mmole), 2-(1,3,5-trimethyl-1H-pyrazol-4-yl-isonicotinic acid methyl ester (35 mg, 0.145 mmole), and tetrahydrofuran (3 ml) was cooled to −78° C. and reacted in accordance with General procedure J (LDA metallation), followed by work up method D. Thus, lithium diisopropylamide (2N, 0.15 ml, 0.30 mmole) was added slowly to the mixture which was stirred at −78° C. for 2 hours and then quenched with water. Solvent was removed and crude product was purified by using HPLC to afford [5-(4-dimethylamino-piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl]-[2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-pyridin-4-yl]-methanone (3 mg, 4.5%) as a yellow solid. 1H NMR (400 MHz, CD3OD) δ 1.57 (m, 2H), 1.99 (m, 2H), 2.33 (s, 6H), 2.35 (s, 3H), 2.43 (s, 3H), 2.90 (m, 2H), 3.14 (m, 1H), 3.81 (s, 3H), 4.49 (m, 2H), 6.90 (d, J=9.03 Hz, 1H), 7.85 (d, J=9.03 Hz, 1H), 7.95 (d, J=5.02 Hz, 1H), 8.11 (s, 1H), 8.78 (d, J=5.02 Hz, 1H). MS(ESI) m/z 459 [M+1].
Workup
- customquenched with water
- customSolvent was removed
- customcrude product was purified
Sources & evidence
- ORD record
- ord-6ca545eafc13491a960461a162c4895c
- Source dataset
- uspto-grants-2013_12
- Patent number
- US08598217B2
Reaction notes
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