1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 135481021, compound

HRID 2111183Notes

Reaction equation

HRID 2111183 reaction equation
[OH:1][CH2:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([C:12]1[C:13]3[S:19][C:18]([C:20]([OH:22])=O)=[CH:17][C:14]=3[NH:15][N:16]=1)=[CH:6]2.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[F:53][C:54]1[CH:59]=[CH:58][C:57]([N:60]2[CH2:65][CH2:64][NH:63][CH2:62][CH2:61]2)=[CH:56][CH:55]=1>CN(C)C=O.C(OCC)(=O)C.CO>[F:53][C:54]1[CH:55]=[CH:56][C:57]([N:60]2[CH2:65][CH2:64][N:63]([C:20]([C:18]3[S:19][C:13]4[C:12]([C:7]5[NH:8][C:9]6[C:5]([CH:6]=5)=[CH:4][C:3]([CH2:2][OH:1])=[CH:11][CH:10]=6)=[N:16][NH:15][C:14]=4[CH:17]=3)=[O:22])[CH2:62][CH2:61]2)=[CH:58][CH:59]=1

Participants

9

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 752601-(4-Fluorophenyl)piperazineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 135442621HCID 135442621, compound

Product 1

HCID 135481021HCID 135481021, compoundYield 58.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-(5-hydroxymethyl-1H-indol-2-yl)-1H-thieno[3,2-c]pyrazole-5-carboxylic acid [124 mg, 0.396 mmol, Example (37)] in dimethyl formamide (5 mL) is added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (91 mg, 0.474 mmol) and 1-hydroxybenzotriazole (54 mg, 0.399 mmol). After stirring for 10 minutes, to it is added diisopropylethylamine (0.138 mL) and 1-(4-fluorophenyl)piperazine (79 mg, 0.438 mmol). The resulting yellow solution mixture is stirred at room temperature overnight. The reaction mixture is diluted in ethyl acetate (60 mL) and washed with water (3×10 mL), brine and dried over sodium sulfate. Purification by chromatography on silica gel (50% ethyl acetate/heptane then ethyl acetate) gave solid. The solid is redissolved in methanol and triturated with water to give [4-(4-fluoro-phenyl)-piperazin-1-yl]-[3-(5-hydroxymethyl-1H-indol-2-yl)-1H-thieno[3,2-c]pyrazol-5-yl]-methanone [110 mg, 56%, Example (38)] as cream solid, mp=156-158° C.; 1H NMR [(CD3)2SO)]: δ 13.490 (1H, s), 11.59 (1H, s), 7.563 (2H), 7.356 (1H), 7.109-6.985 (5H, m), 6.648 (1H), 5.004 (1H, t, OH), 4.553 (2H, d, OCH2), 3.856 (4H, br s), 3.208 (4H, br peak); LC/MS: 476 (M+H).

Workup

  1. stirringThe resulting yellow solution mixture is stirred at room temperature overnight
  2. washwashed with water (3×10 mL), brine
  3. dry with materialdried over sodium sulfate
  4. customPurification by chromatography on silica gel (50% ethyl acetate/heptane
  5. customethyl acetate) gave solid
  6. customtriturated with water

Sources & evidence

ORD record
ord-73648e597fed4b4aa231ee650bfb520b
Source dataset
uspto-grants-2009_04
Patent number
US07518000B2

Reaction notes

Loading…