Diisopropylethylamine → HCID 86762151, compound

HRID 1907413Notes

Reaction equation

HRID 1907413 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([OH:10])=O)=[N:6][CH:7]=1.[NH2:11][C:12]1[CH:13]=[CH:14][C:15]([F:35])=[C:16]([C@:18]23[O:26][CH2:25][CH2:24][C@H:23]2[CH2:22][S:21][C:20]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[N:19]3)[CH:17]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.O>[F:35][C:15]1[CH:14]=[CH:13][C:12]([NH:11][C:8](=[O:10])[C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][N:6]=2)=[CH:17][C:16]=1[C@:18]12[O:26][CH2:25][CH2:24][C@H:23]1[CH2:22][S:21][C:20]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:32])([CH3:31])[CH3:33])=[N:19]2

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 27628765-fluoropyridine-2-carboxylic AcidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86762143HCID 86762143, compound

Product 1

HCID 86762151HCID 86762151, compoundYield 40.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 5-fluoropicolinic acid (6.34 mg, 0.045 mmol), tert-butyl ((4aR,7aR)-7a-(5-amino-2-fluorophenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-yl)carbamate (11 mg, 0.030 mmol), HATU (17.07 mg, 0.045 mmol), Hunig's Base (10.46 μL, 0.060 mmol) in DMF (299 μL) was stirred at rt for 10 h. The crude reaction mixture was purified by reverse phase preparative HPLC on a Luna C18 column (10 μM, 30×100 mm) eluting with 0-100% B (A: 95% eater/5% MeCN/10 nM NH4OAc, B: 5% water/95% MeCN/10 mM NH4OAc) over 12 min to give tert-butyl ((4aR,7aR)-7a-(2-fluoro-5-(5-fluoropicolinamido)phenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-yl)carbamate (6 mg, 0.012 mmol, 40.9% yield) as a white solid.

Workup

  1. customThe crude reaction mixture
  2. customwas purified by reverse phase preparative HPLC on a Luna C18 column (10 μM, 30×100 mm)
  3. washeluting with 0-100% B (A: 95% eater/5% MeCN/10 nM NH4OAc, B

Sources & evidence

ORD record
ord-7c8f6e349957404f91f27787da6c0fdf
Source dataset
uspto-grants-2013_12
Patent number
US08598161B2

Reaction notes

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