Phosphorus oxychloride → HCID 66749241, compound

HRID 2402164Notes

Reaction equation

HRID 2402164 reaction equation
[N:1]1([C:7]2[S:8][C:9]([C:23]([NH2:25])=O)=[C:10]([CH2:12][C:13]3[CH:22]=[CH:21][C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[CH:14]=3)[N:11]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.P(Cl)(Cl)(Cl)=O>>[N:1]1([C:7]2[S:8][C:9]([C:23]#[N:25])=[C:10]([CH2:12][C:13]3[CH:22]=[CH:21][C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[CH:14]=3)[N:11]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 66749979HCID 66749979, compound

Product 1

HCID 66749241HCID 66749241, compoundYield 98%

Conditions

Temperature
80 °C

Procedure

A mixture of 2-(morpholin-4-yl)-4-(2-naphthylmethyl)-1,3-thiazole-5-carboxamide (229 mg, 0.648 mmol) (for amide coupling, see example 61-step 1) and phosphoryl chloride (4.00 mL, 42.9 mmol) was stirred at 80° C. for 30 min. The reaction slowly turned homogeneous. The resulting solution was concentrated under reduced pressure and carefully quenched with 1N NaOH solution at 0° C. The resulting mixture was distributed between 1N NaOH solution and EtOAc. The aqueous layer was extracted with EtOAc. The combined organic layer was dried and concentrated to provide 2-(morpholin-4-yl)-4-(2-naphthylmethyl)-1,3-thiazole-5-carbonitrile as a yellow solid (213 mg, 98.0% yield). LCMS: (AA) ES+ 336; 1H NMR (400 MHz, DMSO) δ 7.90-7.83 (dd, J=9.0, 1.9 Hz, 3H), 7.80-7.72 (s, 1H), 7.53-7.46 (m, 2H), 7.46-7.38 (m, 1H), 4.18-4.09 (s, 2H), 3.70-3.60 (t, J=4.9 Hz, 4H), 3.51-3.41 (t, J=4.9 Hz, 4H).

Workup

  1. customThe reaction slowly turned homogeneous
  2. concentrationThe resulting solution was concentrated under reduced pressure
  3. customcarefully quenched with 1N NaOH solution at 0° C
  4. extractionThe aqueous layer was extracted with EtOAc
  5. customThe combined organic layer was dried
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-6610de4283d14ae1b067e54ee03fb4b2
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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