Phosphorus oxychloride → HCID 90416715, compound

HRID 1498881Notes

Reaction equation

HRID 1498881 reaction equation
O[C:2]1[C:7]2[S:8][CH:9]=[C:10]([C:11]3[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=3)[C:6]=2[C:5](=[O:17])[N:4]([CH3:18])[N:3]=1.O=P(Cl)(Cl)[Cl:21]>>[Cl:21][C:2]1[C:7]2[S:8][CH:9]=[C:10]([C:11]3[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=3)[C:6]=2[C:5](=[O:17])[N:4]([CH3:18])[N:3]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178481941HCID 178481941, compound

Product 1

HCID 90416715HCID 90416715, compound

Conditions

Temperature
120 °C

Procedure

The mixture of 7-hydroxy-5-methyl-3-(pyridin-4-yl)thieno[2,3-d]pyridazin-4(5H)-one and 4-hydroxy-6-methyl-3-(pyridin-4-yl)thieno[2,3-d]pyridazin-7(5H)-one (2.0 g, 7.71 mmol) was dissolved in POCl3 (15 mL) and stirred at 120° C. for about 18 h. Following this, most of the solvent was removed under reduced pressure. Water was added in caution until the POCl3 was consumed. MeOH was added, basified with K2CO3. The suspension was filtered through a Büchner funnel. The filtrate was concentrated to dryness under reduced pressure. The resulting brown oil was purified by preparative HPLC to give the title compound as white solid. Preparative HPLC was performed using a 2767 PHW003 HPLC-system (Waters) equipped with a C18 preparative column (10 um 21*250 mm, Boston). Mobile Phase: A: water (10 mM NH4HCO3), B: CH3CN; Gradient: 30-43% B in 8 min, stop at 14 min; Flow Rate: 30 mL/min; Detective Wavelength: 214\254 nm; Rt: 5.77 mM. LC-MS (Method B): m/z 278 (M+H)+, Rt: 1.79 min. 1H NMR (400 MHz, CDCl3): δ=8.69-7.68 (m, 2H), 7.67 (s, 1H), 7.49-7.48 (m, 2H), 3.82 (s, 1H).

Workup

  1. customwas removed under reduced pressure
  2. additionWater was added in caution until the POCl3
  3. customwas consumed
  4. additionMeOH was added
  5. filtrationThe suspension was filtered through a Büchner funnel
  6. concentrationThe filtrate was concentrated to dryness under reduced pressure
  7. customThe resulting brown oil was purified by preparative HPLC

Sources & evidence

ORD record
ord-19fa178c9837427b9a2c53ead55c9ec8
Source dataset
uspto-grants-2015_12
Patent number
US09200005B2

Reaction notes

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