Dimethylformamide → (S)-tert-Butyl (2-(benzyloxy)-5-(((3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)carbamoyl)pyridin-3-yl)carbamate

HRID 509406Notes

Reaction equation

HRID 509406 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([NH:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=NC=C(C=1)C(O)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[F:27][C:28]1[CH:29]=[C:30]([C@@H:39]([C:41]2[C:46]([F:47])=[CH:45][CH:44]=[CH:43][N:42]=2)[NH2:40])[CH:31]=[CH:32][C:33]=1[O:34][C:35]([F:38])([F:37])[F:36].CN(C(ON1N=NC2[CH:59]=[CH:60][CH:61]=[N:62]C1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.CN([CH:84]=[O:85])C>O.CCOC(C)=O>[CH2:1]([O:8][C:9]1[C:10]([NH:18][C:19](=[O:20])[O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[CH:59][C:60]([C:84](=[O:85])[NH:40][C@@H:39]([C:30]2[CH:31]=[CH:32][C:33]([O:34][C:35]([F:38])([F:37])[F:36])=[C:28]([F:27])[CH:29]=2)[C:41]2[C:46]([F:47])=[CH:45][CH:44]=[CH:43][N:42]=2)=[CH:61][N:62]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 711443205-(Benzyloxy)-6-((tert-butoxycarbonyl)amino)nicotinic AcidHCID 86687985(S)-(3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methanamine hydrochloride2×

Product 1

HCID 86687990(S)-tert-Butyl (2-(benzyloxy)-5-(((3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)carbamoyl)pyridin-3-yl)carbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 5-(benzyloxy)-6-((tert-butoxycarbonyl)amino)nicotinic acid (800 mg, 0.0023 mol) in DMF (10 mL), were added (S)-(3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methanamine hydrochloride (790 mg, 0.0023 mol, Intermediate 6), HATU (1.325 g, 0.0034 mol) and DIPEA (900 mg, 0.0069 mol). The reaction mixture was then stirred for 12 h at rt. Reaction progress was monitored by TLC (100% EtOAc). After completion of the reaction, water (8 mL) was added, and the aqueous solution was extracted with EtOAc (5 mL×3) and concentrated to provide the product. The product thus obtained was purified by column chromatography, silica gel (100-200 mesh), using 80-100% EtOAc in petroleum ether as the eluent to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ: 9.52 (d, J=7.6 Hz, 1H), 9.10 (s, 1H), 8.47 (t, 7.5 Hz, 2H), 7.93 (d, J=1.8 Hz, 1H), 7.82 (dd, 0.9, 9.6 Hz, 1H), 7.63-7.46 (m, 4H), 7.40-7.33 (m, 4H), 6.75 (d, J=7.8 Hz, 1H), 5.20 (s, 2H), 1.40 (s, 9H).

Workup

  1. customReaction progress
  2. additionwas added
  3. extractionthe aqueous solution was extracted with EtOAc (5 mL×3)
  4. concentrationconcentrated
  5. customto provide the product
  6. customThe product thus obtained
  7. customwas purified by column chromatography, silica gel (100-200 mesh)

Sources & evidence

ORD record
ord-03c5e0b88d7c4103b08caacc91557e79
Source dataset
uspto-grants-2015_08
Patent number
US09096527B2

Reaction notes

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