Diisopropylethylamine → HCID 86762149, compound

HRID 1907411Notes

Reaction equation

HRID 1907411 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([C:9]([OH:11])=O)=[N:7][CH:8]=1)#[N:2].[NH2:12][C:13]1[CH:14]=[CH:15][C:16]([F:36])=[C:17]([C@@:19]23[O:27][CH2:26][CH2:25][C@@H:24]2[CH2:23][S:22][C:21]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[N:20]3)[CH:18]=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>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([C:9]([NH:12][C:13]2[CH:14]=[CH:15][C:16]([F:36])=[C:17]([C@@:19]34[O:27][CH2:26][CH2:25][C@@H:24]3[CH2:23][S:22][C:21]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:32])([CH3:33])[CH3:34])=[N:20]4)[CH:18]=2)=[O:11])=[N:7][CH:8]=1)#[N:2]

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 124007345-Cyanopyridine-2-carboxylic acidHCID 86762148HCID 86762148, compound

Product 1

HCID 86762149HCID 86762149, compoundYield 40.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 5-cyanopicolinic acid (6.65 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 12 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-cyanopicolinamido)-2-fluorophenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-yl)carbamate (6 mg, 0.012 mmol, 40.3% yield) as a white solid. 1H NMR (500 MHz, CHLOROFORM-d) δ 9.90 (s, 1H), 8.94 (d, J=1.2 Hz, 1H), 8.45 (d, J=8.1 Hz, 1H), 8.24 (dd, J=8.1, 2.0 Hz, 1H), 8.10-7.97 (m, 1H), 7.72 (d, J=4.0 Hz, 1H), 7.16 (dd, J=10.7, 9.0 Hz, 1H), 4.27-4.06 (m, 2H), 3.32 (d, J=12.7 Hz, 1H), 3.04-2.84 (m, 2H), 2.49-2.34 (m, 1H), 2.23 (td, J=13.0, 7.9 Hz, 1H), 1.51 (s, 9H). MS (M+H)+: 498.20.

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-f0b670fae51a4dfaa12a3a1a4998d56f
Source dataset
uspto-grants-2013_12
Patent number
US08598161B2

Reaction notes

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