Ammonium Chloride → HCID 86634761, compound

HRID 911041Notes

Reaction equation

HRID 911041 reaction equation
[Br-].[CH3:2][N:3]([CH3:26])[CH2:4][CH2:5][CH2:6][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C([Li])CCC.[F:32][C:33]1[CH:54]=[CH:53][CH:52]=[C:51]([F:55])[C:34]=1[O:35][C:36]1[C:41]([CH:42]=O)=[CH:40][N:39]=[C:38]([NH:44][C:45]2[S:46][CH:47]=[C:48]([CH3:50])[N:49]=2)[CH:37]=1.[NH4+].[Cl-:57]>O.C1COCC1>[ClH:57].[ClH:57].[F:32][C:33]1[CH:54]=[CH:53][CH:52]=[C:51]([F:55])[C:34]=1[O:35][C:36]1[C:41]([CH:42]=[CH:6][CH2:5][CH2:4][N:3]([CH3:26])[CH3:2])=[CH:40][N:39]=[C:38]([NH:44][C:45]2[S:46][CH:47]=[C:48]([CH3:50])[N:49]=2)[CH:37]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 15982517[3-(Dimethylamino)propyl](triphenyl)phosphanium bromideHCID 57898918HCID 57898918, compoundHCID 178418339Butyllithium

Product 1

HCID 86634761HCID 86634761, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A flask was charged with (3-(dimethylamino)propyl)triphenylphosphonium bromide (0.555 g, 1.30 mmol) and THF (5 mL) and cooled to 0° C. Butyllithium (0.518 mL, 1.30 mmol) was added. The reaction was stirred at 0° C. for 20 minutes, and then 4-(2,6-difluorophenoxy)-6-(4-methylthiazol-2-ylamino)nicotinaldehyde (Example 146; 0.150 g, 0.432 mmol) was added. The reaction was stirred at ambient temperature overnight. Water and saturated NH4Cl were added, and the reaction was extracted with ethyl acetate and dichloromethane. The organic layer was dried, filtered and concentrated, and the crude material was purified by silica gel column chromatography eluting with DCM-2-5% methanol/DCM. The isolated material was treated with 2M HCl in ether and dried over high vacuum to give the title compound (0.165 mg, 78% yield) as a white solid. 1H NMR (CDCl3) δ 8.43 (s, 0.5H), 8.22 (s, 0.5H), 7.29 (m, 1H), 7.25 (m, 1H), 7.08 (m, 2H), 6.95 (d, 0.5H), 6.68 (d, 0.5H), 6.38 (d, 1H), 6.31 (d, 1H), 3.16 (dt, 2H), 2.87 (s, 6H), 2.79 (m, 2H), 2.32 (d, 3H).

Workup

  1. stirringThe reaction was stirred at ambient temperature overnight
  2. extractionthe reaction was extracted with ethyl acetate and dichloromethane
  3. customThe organic layer was dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customthe crude material was purified by silica gel column chromatography
  7. washeluting with DCM-2-5% methanol/DCM
  8. additionThe isolated material was treated with 2M HCl in ether
  9. customdried over high vacuum

Sources & evidence

ORD record
ord-5dab636f1c4e4c2fb09a058deadcffbc
Source dataset
uspto-grants-2011_09
Patent number
US08022222B2

Reaction notes

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