4-Aminopyridine → HCID 89783665, compound

HRID 1056004Notes

Reaction equation

Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[C:5]([C:12]3[NH:20][C:19]4[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=4[CH:13]=3)[CH:6]=[CH:7][CH:8]=2)[N:3]=1.[N:22]1[CH:27]=[CH:26][C:25]([NH2:28])=[CH:24][CH:23]=1.CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>>[N:22]1[CH:27]=[CH:26][C:25]([NH:28][C:2]2[CH:11]=[CH:10][C:9]3[C:4](=[C:5]([C:12]4[NH:20][C:19]5[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=5[CH:13]=4)[CH:6]=[CH:7][CH:8]=3)[N:3]=2)=[CH:24][CH:23]=1

Participants

Reactant 4

HCID 17274-Aminopyridine

HCID 2733832Lithium Hexamethyldisilazide

HCID 25112535Brettphos2×

HCID 897835482-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 1

HCID 89783665HCID 89783665, compoundYield 13%

Conditions

Temperature: 150 °C

Procedure

Prepared similarly to that described in Example 82 using 2-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 1; 58 mg, 0.195 mmol), pyridin-4-amine (22.00 mg, 0.234 mmol, Aldrich), BrettPhos precat (Strem, Newburyport, Mass.; 8.25 mg, 9.74 μmmol), Brettphos (Strem, Newburyport, Mass.; 5.70 mg, 9.74 μmmol), and LHMDS (1.0M in THF; 429 μl, 0.429 mmol), heating at 150° C. for 40 min in a microwave (Biotage Initiator). Purification by silica gel chromatography (100% DCM to 10% MeOH/DCM) provided 2-(2-(pyridin-4-ylamino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (13% yield). 1H NMR (400 MHz, MeOH-d4) δ ppm 2.85 (t, J=7.04 Hz, 2H) 3.62 (t, J=7.04 Hz, 2H) 6.99 (s, 1H) 7.11 (d, J=9.00 Hz, 1H) 7.39 (t, J=7.73 Hz, 1H) 7.64 (dd, J=8.02, 1.17 Hz, 1H) 7.75 (d, J=6.46 Hz, 2H) 7.94 (dd, J=7.43, 1.17 Hz, 1H) 8.14 (d, J=8.80 Hz, 1H) 8.33 (d, J=6.26 Hz, 2H). MS (ESI, pos. ion) m/z: 356.3 (M+1).

Workup

customPrepared similarly to
customPurification by silica gel chromatography (100% DCM to 10% MeOH/DCM)

Sources & evidence

ORD record: ord-5ea33be48ee74cb48cb619ae69eefc34
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394297B2

Reaction notes

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