Trifluoroacetic acid methylene chloride → N-(4-((1R,3R,5S)-3-amino-5-methyl-4-oxocyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide

HRID 705287Notes

Reaction equation

HRID 705287 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[N:14]=[C:13]([C:15]([NH:17][C:18]2[CH:19]=[N:20][CH:21]=[CH:22][C:23]=2[C@H:24]2[CH2:29][C@@H:28]([NH:30]C(=O)OC(C)(C)C)[C:27](=[O:38])[C@@H:26]([CH3:39])[CH2:25]2)=[O:16])[CH:12]=[CH:11][C:10]=1[F:40].C(O)(C(F)(F)F)=O.C(Cl)Cl>>[NH2:30][C@H:28]1[C:27](=[O:38])[C@@H:26]([CH3:39])[CH2:25][C@@H:24]([C:23]2[CH:22]=[CH:21][N:20]=[CH:19][C:18]=2[NH:17][C:15](=[O:16])[C:13]2[CH:12]=[CH:11][C:10]([F:40])=[C:9]([C:3]3[C:4]([F:8])=[CH:5][CH:6]=[CH:7][C:2]=3[F:1])[N:14]=2)[CH2:29]1

Participants

3

Reactant 2

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 86705245tert-butyl (1R,3S,5R)-5-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-3-methyl-2-oxocyclohexylcarbamate

Product 1

HCID 72549148N-(4-((1R,3R,5S)-3-amino-5-methyl-4-oxocyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamideYield 98%

Procedure

Tert-butyl (1R,3S,5R)-5-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-3-methyl-2-oxocyclohexylcarbamate was treated with 25% TFA/CH2Cl2 for 30 minutes. The volatiles were removed in vacuo, the residue was dissolved in DMSO and purified by reverse phase HPLC to yield N-(4-((1R,3R,5S)-3-amino-5-methyl-4-oxocyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide in 98% yield. LC/MS (m/z)=455.1 (MH+), Rt=0.57 min. 1H NMR (300 MHz, DMSO-d6) δ ppm 10.55 (s, 1H), 8.55 (s, 1H), 8.47 (d, J=4.0, 1H), 8.37 (dd, J=8.0, 4.0, 1H), 8.21 (t, J=8.0, 1H), 8.16 (broad doublet, J=4.0, 2H), 7.67-7.74 (m, 1H), 7.40 (d, J=8.0, 1H), 7.36 (t, J=8.0, 2H), 4.20-4.26 (m, 1H), 3.50-3.70 (m, 2H), 2.76-2.82 (m, 1H), 2.49-2.54 (m, 1H), 2.32-2.36 (m, 1H), 2.16-2.18 (m, 1H), 1.91 (q, J=12, 1H), 1.65 (q, J=12, 1H), 0.97 (d, J=8.0, 3H).

Workup

  1. customThe volatiles were removed in vacuo
  2. dissolutionthe residue was dissolved in DMSO
  3. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-e12eb1aaf09e420fae7a1ddc09b5cbf0
Source dataset
uspto-grants-2015_11
Patent number
US09173883B2

Reaction notes

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