2-Bromo-3,5,6-trifluoropyridine → (R)-ethyl 3-((6-bromo-3,5-difluoropyridin-2-yl)amino)-4,4-dimethylpentanoate

HRID 1055117Notes

Reaction equation

HRID 1055117 reaction equation
[F:1][C:2]1[C:3]([NH:18][CH:19]([C:24]2([CH3:29])[CH2:28]CC[CH2:25]2)[CH2:20][C:21]([OH:23])=[O:22])=[N:4][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([F:17])[CH:15]=3)[NH:10][N:9]=2)=NC=1.[Br:30][C:31]1[N:36]=[C:35]([NH:37][C@@H:38]([C:45]([CH3:48])([CH3:47])[CH3:46])[CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41])[C:34]([F:49])=[CH:33][C:32]=1[F:50].ClC1N=C(N[C@@H](C2(C)CCCC2)CC(OCC)=O)C(F)=CC=1C#N.BrC1C(F)=CC(F)=C(F)N=1.ClC1C(C#N)=CC(F)=C(F)N=1>C(#N)C.C(O)=O>[F:1][C:2]1[C:3]([NH:18][C@@H:19]([C:24]([CH3:28])([CH3:29])[CH3:25])[CH2:20][C:21]([OH:23])=[O:22])=[N:4][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([F:17])[CH:15]=3)[NH:10][N:9]=2)=[C:34]([F:49])[CH:33]=1.[Br:30][C:31]1[N:36]=[C:35]([NH:37][C@@H:38]([C:45]([CH3:47])([CH3:46])[CH3:48])[CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41])[C:34]([F:49])=[CH:33][C:32]=1[F:50]

Participants

9

Reactant 5

HCID 457907252-Bromo-3,5,6-trifluoropyridineHCID 735548082-Chloro-5,6-difluoronicotinonitrileHCID 86714767(R)-ethyl 3-(6-chloro-5-cyano-3-fluoropyridin-2-ylamino)-3-(1-methylcyclopentyl)propanoateHCID 86714771(R)-ethyl 3-((6-bromo-3,5-difluoropyridin-2-yl)amino)-4,4-dimethylpentanoateHCID 178427251HCID 178427251, compound

Product 2

HCID 86714771(R)-ethyl 3-((6-bromo-3,5-difluoropyridin-2-yl)amino)-4,4-dimethylpentanoateHCID 178445894HCID 178445894, compound

Reagents, catalysts & solvents 2

HCID 284Formic AcidSolventHCID 6342AcetonitrileSolvent

Procedure

Compound 6 was synthesized in a manner similar to compound 12, utilizing (R)-ethyl 3-((6-bromo-3,5-difluoropyridin-2-yl)amino)-4,4-dimethylpentanoate as the intermediate for the Suzuki coupling. (R)-ethyl 3-((6-bromo-3,5-difluoropyridin-2-yl)amino)-4,4-dimethyl-pentanoate was prepared in the same fashion as intermediate, 143a, utilizing 2-bromo-3,5,6-trifluoropyridine as the starting material instead of 2-chloro-5,6-difluoropyridine-3-carbonitrile: 1H NMR (400 MHz, CDCl3) δ 8.31 (d, J=6.4 Hz, 1H), 8.06 (s, 1H), 7.06 (t, J=9.7 Hz, 1H), 4.58 (s, 2H), 2.80 (d, J=13.2 Hz, 1H), 2.29 (dd, J=13.3, 8.7 Hz, 1H), 0.98 (s, 9H); LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, Retention Time=2.92 min, (M+H) 394.19.

Sources & evidence

ORD record
ord-3305ff0ae1334ab7926ca4353052ec13
Source dataset
uspto-grants-2016_07
Patent number
US09394302B2

Reaction notes

Loading…