Diisopropylethylamine → HCID 86762154, compound

HRID 1907416Notes

Reaction equation

HRID 1907416 reaction equation
[F:1][C:2]1[C:3]([C:8]([OH:10])=O)=[N:4][CH:5]=[CH: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:3]2[C:2]([F:1])=[CH:7][CH:6]=[CH:5][N:4]=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 27627863-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 86762148HCID 86762148, compound

Product 1

HCID 86762154HCID 86762154, compoundYield 40.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 3-fluoropicolinic acid (6.34 mg, 0.045 mmol), tert-butyl ((4aS,7aS)-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), and Hunig's Base (10.46 μL, 0.060 mmol) in DMF (299 μL) was stirred at rt for 10 h. The crude product 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 ((4aS,7aS)-7a-(2-fluoro-5-(3-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. 1H NMR (500 MHz, CHLOROFORM-d) δ 9.91 (br. s., 1H), 8.49 (br. s., 1H), 8.11-7.97 (m, 1H), 7.71 (d, J=5.2 Hz, 1H), 7.68-7.61 (m, 1H), 7.61-7.55 (m, 1H), 7.17-7.10 (m, 1H), 4.27-4.06 (m, 2H), 3.33 (d, J=13.4 Hz, 1H), 3.03 (d, J=13.7 Hz, 1H), 2.90 (dd, J=13.0, 4.5 Hz, 1H), 2.47-2.33 (m, 1H), 2.29-2.15 (m, 1H), 1.51 (s, 9H). MS (M+H)+: 491.19.

Workup

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

Sources & evidence

ORD record
ord-7b9cce617a9c460882ee5d61e7877ac7
Source dataset
uspto-grants-2013_12
Patent number
US08598161B2

Reaction notes

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