Diisopropylethylamine → (+)-2-chloromethyl-N-(7-[1,4]dioxan-2-yl-4-methoxy-benzothiazol-2-yl)-isonicotinamide

HRID 985808Notes

Reaction equation

HRID 985808 reaction equation
[Cl:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][N:11]=1)[C:6]([OH:8])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)C(C)C)C.[O:45]1[CH2:50][CH2:49][O:48][CH2:47][CH:46]1[C:51]1[C:59]2[S:58][C:57]([NH2:60])=[N:56][C:55]=2[C:54]([O:61][CH3:62])=[CH:53][CH:52]=1.C(=O)(O)[O-].[Na+]>C1COCC1>[Cl:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][N:11]=1)[C:6]([NH:60][C:57]1[S:58][C:59]2[C:51]([CH:46]3[CH2:47][O:48][CH2:49][CH2:50][O:45]3)=[CH:52][CH:53]=[C:54]([O:61][CH3:62])[C:55]=2[N:56]=1)=[O:8]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 222522422-(Chloromethyl)isonicotinic acidHCID 22507697(+)-7-[1,4)Dioxan-2-yl-4-methoxy-benzothiazol-2-ylamine

Product 1

HCID 22507718(+)-2-chloromethyl-N-(7-[1,4]dioxan-2-yl-4-methoxy-benzothiazol-2-yl)-isonicotinamideYield 48%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 503 mg (2.93 mmol) 2-chloromethyl-isonicotinic acid in 50 ml THF were added 1.28 g (3.38 mmol) HATU and 0.96 ml (5.63 mmol) N-ethyldiisopropylamine and stirring continued at room temperature for 2 h. 600 mg (2.25 mmol) (+)-7-[1,4]dioxan-2-yl-4-methoxy-benzothiazol-2-ylamine was then added and stirring continued at room temperature for 24 h. The reaction mixture was then poured into saturated aqueous sodium bicarbonate solution and extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated in vacuo. Flash chromatography (acetone) followed by trituration in ether afforded 450 mg (48%) (+)-2-chloromethyl-N-(7-[1,4]dioxan-2-yl-4-methoxy-benzothiazol-2-yl)-isonicotinamide as a light yelllow solid. [α]D20=+12.1° (c=0.41, CHCl3), ES-MS m/e (%):422 (M{37Cl}+H+, 35), 420 (M{35Cl}+H+, 100).

Workup

  1. stirringstirring
  2. waitcontinued at room temperature for 24 h
  3. extractionextracted three times with ethyl acetate
  4. dry with materialThe combined organic phases were dried over sodium sulfate
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d48f015c53224fdca28ae3127ed71510
Source dataset
uspto-grants-2005_03
Patent number
US06872833B2

Reaction notes

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