2-Aminopyridine → HCID 89783286, compound

HRID 1056005Notes

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][CH:25]=[CH:24][C:23]=1[NH2:28].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][CH:25]=[CH:24][C:23]=1[NH:28][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

Participants

Reactant 4

HCID 104392-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 89783286HCID 89783286, compoundYield 29%

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; 154 mg, 0.517 mmol), pyridin-2-amine (58.4 mg, 0.621 mmol, Aldrich), BrettPhos precat (Strem, Newburyport, Mass.; 21.90 mg, 0.026 mmol), Brettphos (Strem, Newburyport, Mass.; 15.12 mg, 0.026 mmol), and LHMDS (1.0M in THF; 1138 μl, 1.138 mmol), heating at 150° C. for 30 min in a microwave reactor (Biotage Initiator). Purification by silica gel (100% DCM to 5% MeOH/DCM) provided 2-(2-(pyridin-2-ylamino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (29% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.92 (t, J=6.75 Hz, 2H) 3.45 (td, J=6.80, 2.25 Hz, 2H) 6.96 (br. s., 1H) 6.99 (d, J=2.15 Hz, 1H) 7.02 (dd, J=6.85, 5.48 Hz, 1H) 7.36 (t, J=7.73 Hz, 1H) 7.54 (d, J=8.80 Hz, 1H) 7.58 (d, J=8.22 Hz, 1H) 7.63 (d, J=7.24 Hz, 1H) 7.76 (td, J=6.85, 1.96 Hz, 1H) 8.02 (dd, J=6.46, 0.98 Hz, 1H) 8.20 (d, J=9.00 Hz, 1H) 8.41 (dd, J=4.89, 1.37 Hz, 1H) 10.16 (s, 1H) 12.72 (br. s., 1H). MS (ESI, pos. ion) m/z: 356.1 (M+1).

Workup

customPrepared similarly to
customPurification by silica gel (100% DCM to 5% MeOH/DCM)

Sources & evidence

ORD record: ord-89703f303cd941a7899e954afcac1bc3
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394297B2

Reaction notes

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