Diisopropylethylamine → 4-(4-cyclopropylethynyl-2-oxo-4-trifluoromethyl-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yloxy)-butyric Acid 2,5-dioxo-pyrrolidin-1-yl Ester

HRID 29017Notes

Reaction equation

HRID 29017 reaction equation
[CH:1]1([C:4]#[C:5][C:6]2([C:24]([F:27])([F:26])[F:25])[O:11][C:10](=[O:12])[NH:9][C:8]3[CH:13]=[CH:14][C:15]([O:17][CH2:18][CH2:19][CH2:20][C:21]([OH:23])=[O:22])=[CH:16][C:7]2=3)[CH2:3][CH2:2]1.C(N(CC)C(C)C)(C)C.[B-](F)(F)(F)F.CN(C(O[N:50]1[C:55](=[O:56])[CH2:54][CH2:53][C:51]1=[O:52])=[N+](C)C)C>C1COCC1>[O:52]=[C:51]1[CH2:53][CH2:54][C:55](=[O:56])[N:50]1[O:22][C:21](=[O:23])[CH2:20][CH2:19][CH2:18][O:17][C:15]1[CH:14]=[CH:13][C:8]2[NH:9][C:10](=[O:12])[O:11][C:6]([C:5]#[C:4][CH:1]3[CH2:3][CH2:2]3)([C:24]([F:27])([F:26])[F:25])[C:7]=2[CH:16]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 98575222-(2,5-Dioxopyrrolidin-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborateHCID 68801865HCID 68801865, compound

Product 1

HCID 875797654-(4-cyclopropylethynyl-2-oxo-4-trifluoromethyl-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yloxy)-butyric Acid 2,5-dioxo-pyrrolidin-1-yl Ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 35 mg (0.091 mmol) of the acid 11 in 2 mL of anhydrous THF was cooled to 0° C., and 30 μL (0.15 mmol) of N,N-diisopropylethylamine was added followed by 40 mg (1.28 mmol) of O-(N-succinimidyl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate. The reaction mixture was allowed to warm up to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by RP preparative HPLC using acetonitrile and water as a mobile phase containing 0.1% of trifluoroacetic acid to give 30 mg (00.62 mmol, 68%) of 12 as a white powder [LC-MS; M+H 481.0].

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe residue was purified by RP preparative HPLC
  3. additioncontaining 0.1% of trifluoroacetic acid

Sources & evidence

ORD record
ord-c1c77d9c5a6c4e7faae283dd05838a0b
Source dataset
uspto-grants-2008_09
Patent number
US07420043B2

Reaction notes

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