2,6-Difluoroaniline → HCID 89783989, compound

HRID 1055987Notes

Reaction equation

HRID 1055987 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.[F:22][C:23]1[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[C:24]=1[NH2:25].CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C>>[F:22][C:23]1[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[C:24]=1[NH:25][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

4

Reactant 3

HCID 796472,6-DifluoroanilineHCID 25112535Brettphos2×HCID 897835482-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 1

HCID 89783989HCID 89783989, compoundYield 22%

Conditions

Temperature
100 °C

Procedure

Prepared similarly to Example 82 using 2-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 1; 51 mg, 0.171 mmol), 2,6-difluoroaniline (26.5 mg, 0.206 mmol, Aldrich), BrettPhos (Strem, Newburyport, Mass.; 5.0 mg, 8.56 μmol), and BrettPhos precat (Strem, Newburyport, Mass.; 7.3 mg, 8.56 μmol), heating at 100° C. for 3 h. Purification by silica gel (100% DCM to 20% MeOH/DCM) provided 2-(2-((2,6-difluorophenyl)amino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (22% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.47 (t, J=6.75 Hz, 2H) 3.33-3.39 (m, 2H) 6.91-6.95 (m, 2H) 7.14 (d, J=9.00 Hz, 1H) 7.28-7.32 (m, 1H) 7.33 (d, J=4.50 Hz, 1H) 7.35-7.40 (m, 1H) 7.44-7.54 (m, 1H) 7.62 (d, J=6.85 Hz, 1H) 8.01-8.06 (m, 1H) 8.18 (d, J=9.00 Hz, 1H) 9.31 (s, 1H) 11.90 (br. s., 1H). 19F NMR (376 MHz, DMSO-d6) δ ppm −117.35 (2F, s). MS (ESI, pos. ion) m/z: 391.2 (M+1).

Workup

  1. customPurification by silica gel (100% DCM to 20% MeOH/DCM)

Sources & evidence

ORD record
ord-186fe2a2967147e5876b3f47dbb52c94
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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