1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (R)-methyl 3-(pyrazolo[1,5-a]pyrimidine-3-carboxamido)-2,3-dihydro-1H-indene-5-carboxylate

HRID 1193268Notes

Reaction equation

HRID 1193268 reaction equation
[N:1]1[N:5]2[CH:6]=[CH:7][CH:8]=[N:9][C:4]2=[C:3]([C:10]([OH:12])=O)[CH:2]=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.Cl.[CH3:44][O:45][C:46]([C:48]1[CH:49]=[C:50]2[C:54](=[CH:55][CH:56]=1)[CH2:53][CH2:52][C@H:51]2[NH2:57])=[O:47]>ClCCl.C(OCC)(=O)C>[N:1]1[N:5]2[CH:6]=[CH:7][CH:8]=[N:9][C:4]2=[C:3]([C:10]([NH:57][C@H:51]2[C:50]3[C:54](=[CH:55][CH:56]=[C:48]([C:46]([O:45][CH3:44])=[O:47])[CH:49]=3)[CH2:53][CH2:52]2)=[O:12])[CH:2]=1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 1910189Pyrazolo[1,5-a]pyrimidine-3-carboxylic acidHCID 66700566(R)-methyl 3-amino-2,3-dihydro-1H-indene-5-carboxylate hydrochloride

Product 1

HCID 66798613(R)-methyl 3-(pyrazolo[1,5-a]pyrimidine-3-carboxamido)-2,3-dihydro-1H-indene-5-carboxylate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (0.25 g, 1.533 mmol, 1 eq) was dissolved in dichloromethane (20 ml), and the mixture was cooled to 0° C. Then DIPEA (0.65 ml, 2.833 mmol, 2.5 eq), EDCI (0.34 g, 1.84 mmol, 1.2 eq) and HOBT (29 mg, 0.307 mmol, 0.2 eq) were added in succession and stirring was carried out for 15 min at RT. The reaction solution was cooled to 0° C. again, (3R)-3-amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester hydrochloride (A-01) (0.34 g, 1.533 mmol, 1 eq), dissolved in dichloromethane (10 ml), was added, and the mixture was stirred for 16 h at RT. After monitoring by thin-layer chromatography, the reaction solution was diluted with ethyl acetate, washed in succession with 10% NH4Cl solution, sat. NaHCO3 solution and sat. NaCl solution (in each case 20 ml), dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel, ethyl acetate:cyclohexane 2:1) and the desired product (R)-methyl 3-(pyrazolo[1,5-a]pyrimidine-3-carboxamido)-2,3-dihydro-1H-indene-5-carboxylate (B-07) was thus obtained. Yield: 85%

Workup

  1. temperatureThe reaction solution was cooled to 0° C. again
  2. additionwas added
  3. stirringthe mixture was stirred for 16 h at RT
  4. washwashed in succession with 10% NH4Cl solution, sat. NaHCO3 solution and sat. NaCl solution (in each case 20 ml),
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by column chromatography (silica gel, ethyl acetate:cyclohexane 2:1)

Sources & evidence

ORD record
ord-ea24988b430644329cb1dcc1280abc24
Source dataset
uspto-grants-2014_03
Patent number
US08680159B2

Reaction notes

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