Triethylamine → HCID 67540456, compound

HRID 1192438Notes

Reaction equation

HRID 1192438 reaction equation
[ClH:1].Cl.[N:3]1([C:9]2[N:14]=[CH:13][N:12]=[C:11]3[NH:15][N:16]=[CH:17][C:10]=23)[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.C(OC([NH:46][CH2:47][CH2:48][CH:49]([C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=1[Cl:59])[C:50](O)=[O:51])=O)(C)(C)C.C(N(CC)CC)C>CN(C=O)C>[ClH:59].[ClH:1].[NH2:46][CH2:47][CH2:48][CH:49]([C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=1[Cl:59])[C:50]([N:6]1[CH2:5][CH2:4][N:3]([C:9]2[N:14]=[CH:13][N:12]=[C:11]3[NH:15][N:16]=[CH:17][C:10]=23)[CH2:8][CH2:7]1)=[O:51]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 67539793HCID 67539793, compoundHCID 675398394-(1-Piperazinyl)-1H-pyrazolo[3,4-d]pyrimidine dihydrochloride

Product 1

HCID 67540456HCID 67540456, compoundYield 133.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The 4-piperazin-1-yl-1H-pyrazolo[3,4-d]pyrimidine bis-hydrochloride salt (60 mg, 0.22 mmol), HOBt (29 mg, 0.22 mmol), EDCI (46 mg, 0.24 mmol), and 4-tert-butoxycarbonylamino-2-(2-chlorophenyl)-butyric acid [prepared by procedures described in Example 61 (68 mg. 0.22 mmol)] were suspended/dissolved in 1.5 mL of DMF then treated with triethylamine (121 μL, 0.87 mmol). The mixture was allowed to stir for four hours to completion then partitioned between ethyl acetate and diluted NaHCO3 solution. The aqueous was extracted with ethyl acetate, and the organics were combined. The organic was washed with water, brine, separated, dried over MgSO4, filtered, and concentrated in vacuo. The residue was dissolved in 1 mL of 1,4-dioxane and treated with 1 mL of 4M HCl in 1,4-dioxane. The solution stirred overnight to completion at room temperature and diluted with diethyl ether to afford a precipitate. This material was broken up to afford a suspended granular solid which was stirred for 30 minutes. The suspension was filtered, washed with diethyl ether, and dried over a stream of nitrogen to afford the 4-amino-2-(2-chlorophenyl)-1-[4-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-piperazin-1-yl]-butan-1-one bis-hydrochloride salt as a tan solid (69.2 mg, 67%). 1H NMR (D6O, 400 MHz) δ 8.52 (brs, 1H), 8.31 (s, 1H), 7.40 (d, J=7.2 Hz, 1H), 7.12 (m, 3H), 4.42 (t, J=6.8 Hz, 1H), 4.11 (m, 1H), 3.98 (m, 3H), 3.70 (m, 2H), 3.61 (m, 1H), 3.41 (m, 1H), 2.96 (m, 1H), 2.80 (m, 1H), 2.21 (m, 1H), 1.94 (m, 1H). LCMS (APCI+) m/z 400 [M+H]+; Rt=1.52 min.

Workup

  1. customthen partitioned between ethyl acetate and diluted NaHCO3 solution
  2. extractionThe aqueous was extracted with ethyl acetate
  3. washThe organic was washed with water, brine
  4. customseparated
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionThe residue was dissolved in 1 mL of 1,4-dioxane
  9. additiontreated with 1 mL of 4M HCl in 1,4-dioxane
  10. stirringThe solution stirred overnight to completion at room temperature
  11. additiondiluted with diethyl ether
  12. customto afford a precipitate
  13. customto afford a suspended granular solid which
  14. stirringwas stirred for 30 minutes
  15. filtrationThe suspension was filtered
  16. washwashed with diethyl ether
  17. customdried over a stream of nitrogen

Sources & evidence

ORD record
ord-3bf832a094a44364858396b667c5f80d
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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