Phosphorus oxychloride → HCID 59225701, compound

HRID 1426181Notes

Reaction equation

HRID 1426181 reaction equation
[C:1]([NH:4][NH:5][C:6](=O)[CH2:7][CH2:8][C:9]1[N:10]=[C:11]([NH:14][C:15]2[C:20]([O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:19][C:18]([Br:29])=[CH:17][N:16]=2)[S:12][CH:13]=1)(=[O:3])[CH3:2].O=P(Cl)(Cl)Cl>C(#N)C>[CH2:22]([O:21][C:20]1[C:15]([NH:14][C:11]2[S:12][CH:13]=[C:9]([CH2:8][CH2:7][C:6]3[O:3][C:1]([CH3:2])=[N:4][N:5]=3)[N:10]=2)=[N:16][CH:17]=[C:18]([Br:29])[CH:19]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychloride3×HCID 86639707HCID 86639707, compound

Product 1

HCID 59225701HCID 59225701, compoundYield 28.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

The crude N′-acetyl-3-(2-(3-(benzyloxy)-5-bromopyridin-2-ylamino)thiazol-4-yl)propanehydrazide (0.339 g, 0.691 mmol) was added acetonitrile (25 mL), POCl3 (0.380 ml, 4.15 mmol) and the mixture heated at 50° C. overnight. Additional POCl3 (0.5 mL) was added and the reaction was stirred for 3 days 50° C. Additional 0.5 ml POCl3 (0.5 mL) was added and the reaction was stirred at 50° C. for an additional 18 hours. The reaction was then concentrated to dryness, diluted with water, extracted with DCM, dried over Na2SO4, filtered, concentrated to a residue and purified by prep HPLC and then on a silica gel column, eluting with 75% EtOAc/Hexanes, to give 3-(benzyloxy)-5-bromo-N-(4-(2-(5-methyl-1,3,4-oxadiazol-2-yl)ethyl)thiazol-2-yl)pyridin-2-amine (0.092 g, 28% yield) as a white solid. 1H NMR (DMSO-d6) δ 2.44 (s, 3H), 3.01 (t, J=7.6 Hz, 2H), 3.17 (t, J=7.6 Hz, 2H), 5.29 (s, 2H), 6.73 (s, 1H), 7.35 (t, J=7.2 Hz, 1H), 7.42 (t, J=7.2 Hz, 2H), 7.59 (d, J=7.2 Hz, 2H), 7.63 (d, J=1.6 Hz, 1H), 7.97 (d, J=1.8 Hz, 1H), 10.31 (s, 1H); Mass Spectrum (apci) 472 (M+H).

Workup

  1. stirringthe reaction was stirred at 50° C. for an additional 18 hours
  2. concentrationThe reaction was then concentrated to dryness
  3. additiondiluted with water
  4. extractionextracted with DCM
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to a residue
  8. custompurified by prep HPLC
  9. washon a silica gel column, eluting with 75% EtOAc/Hexanes

Sources & evidence

ORD record
ord-bcdcc7c664064366a635de307103f35c
Source dataset
uspto-grants-2015_01
Patent number
US08933077B2

Reaction notes

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