Diisopropylethylamine → HCID 51354790, compound

HRID 2092966Notes

Reaction equation

HRID 2092966 reaction equation
[C:1]1([C:7]#[C:8][C:9]2[S:10][C:11]([C:14]([OH:16])=O)=[CH:12][N:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[F:18][C:19]1([F:25])[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>ClCCl>[F:18][C:19]1([F:25])[CH2:24][CH2:23][N:22]([C:14]([C:11]2[S:10][C:9]([C:8]#[C:7][C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[N:13][CH:12]=2)=[O:16])[CH2:21][CH2:20]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 27583514,4-Difluoropiperidine hydrochlorideHCID 58227488HCID 58227488, compound2×

Product 1

HCID 51354790HCID 51354790, compoundYield 92.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a small culture tube, 2-phenylethynyl-thiazole-5-carboxylic acid (28 mg, 0.12 mmol) [Intermediate 1], 4,4-difluoropiperidine hydrochloride (23 mg, 0.14 mmol) (Oakwood Products, Inc. (West Columbia, S.C., USA) and dichloromethane (1.5 mL) were added. To the mixture, PyBOP® (76 mg, 0.14 mmol) was added, followed by N,N-diisopropylethylamine (63 μL, 0.36 mmol), and the reaction was stirred at room temperature for about 17 hours. Afterwards, the crude reaction mixture was directly purified by Preparative TLC, eluting with 40% EtOAc in hexanes to give 37 mg (92%) of the titled compound, (4,4-difluoro-piperidin-1-yl)-(2-phenylethynyl-thiazol-5-yl)-methanone, as a white solid. 1H NMR (300 MHz, CDCl3) δ 7.99 (s, 1H), 7.66-7.59 (m, 2H), 7.49-7.37 (m, 3H), 3.92-3.82 (m, 4H), 2.18-2.01 (m, 4H). LC/MS (Method 3), RT=1.43 min. Calculated [M+H]+=333; Observed [M+H]+=333.

Workup

  1. customAfterwards, the crude reaction mixture
  2. customwas directly purified by Preparative TLC
  3. washeluting with 40% EtOAc in hexanes

Sources & evidence

ORD record
ord-b6953dd68a2048948f0ee09361dc14d7
Source dataset
uspto-grants-2013_05
Patent number
US08440837B2

Reaction notes

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