Diisopropylethylamine → HCID 86762153, compound

HRID 1907415Notes

Reaction equation

HRID 1907415 reaction equation
[F:1][CH:2]([F:13])[O:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]([OH:12])=O)=[N:8][CH:9]=1.[NH2:14][C:15]1[CH:16]=[CH:17][C:18]([F:38])=[C:19]([C@@:21]23[O:29][CH2:28][CH2:27][C@@H:26]2[CH2:25][S:24][C:23]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[N:22]3)[CH:20]=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:13][CH:2]([F:1])[O:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]([NH:14][C:15]2[CH:16]=[CH:17][C:18]([F:38])=[C:19]([C@@:21]34[O:29][CH2:28][CH2:27][C@@H:26]3[CH2:25][S:24][C:23]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:34])([CH3:35])[CH3:36])=[N:22]4)[CH:20]=2)=[O:12])=[N:8][CH:9]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 574758715-(Difluoromethoxy)picolinic acidHCID 86762148HCID 86762148, compound

Product 1

HCID 86762153HCID 86762153, compoundYield 37.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 5-(difluoromethoxy)picolinic acid (8.49 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-(5-(5-(difluoromethoxy)picolinamido)-2-fluorophenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-yl)carbamate (6 mg, 0.011 mmol, 37.2% yield) as a white solid. 1H NMR (500 MHz, CHLOROFORM-d) δ 9.88 (br. s., 1H), 8.50 (br. s., 1H), 8.34 (d, J=8.7 Hz, 1H), 8.01 (dd, J=9.1, 3.4 Hz, 1H), 7.70 (dd, J=8.6, 2.4 Hz, 2H), 7.19-7.07 (m, 1H), 6.89-6.47 (m, 1H), 4.25-4.07 (m, 2H), 3.33 (d, J=12.7 Hz, 1H), 3.07-2.82 (m, 2H), 2.41 (dd, J=12.8, 7.2 Hz, 1H), 2.29-2.14 (m, 1H), 1.51 (br. s., 9H). MS (M+H)+: 539.22.

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-813fb20b4c7941579f74920f4c630af8
Source dataset
uspto-grants-2013_12
Patent number
US08598161B2

Reaction notes

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