Triethylamine → (S)-2-amino-1-(4-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)piperazin-1-yl)-4-methylpentan-1-one

HRID 1844360Notes

Reaction equation

HRID 1844360 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[CH:9][C:8]([N:11]3[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]3)=[N:7][C:6]=12.[NH:17](C(OC(C)(C)C)=O)[C@H:18]([C:23](O)=[O:24])[CH2:19][CH:20]([CH3:22])[CH3:21].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C=O)C.C(Cl)Cl>[NH2:17][C@@H:18]([CH2:19][CH:20]([CH3:22])[CH3:21])[C:23]([N:14]1[CH2:15][CH2:16][N:11]([C:8]2[CH:9]=[CH:10][N:5]3[N:4]=[CH:3][C:2]([Br:1])=[C:6]3[N:7]=2)[CH2:12][CH2:13]1)=[O:24]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 83170L-Leucine, N-((1,1-dimethylethoxy)carbonyl)-HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 866974343-Bromo-5-(piperazin-1-yl)pyrazolo[1,5-a]pyrimidine

Product 1

HCID 86697446(S)-2-amino-1-(4-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)piperazin-1-yl)-4-methylpentan-1-oneYield 213.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

3-bromo-5-(piperazin-1-yl)pyrazolo[1,5-a]pyrimidine (200 mg, 0.71 mmol), Boc-L-Leu (196 mg, 0.85 mmol), HATU (245 mg, 1.06 mmol), and triethylamine (394 uL, 2.83 mmol) taken up in DMF and stirred at room temperature overnight. Reaction was diluted with DCM and washed with water. The organic layer was dried over magnesium sulfate, filtered and reduced in vacuo. The residue was taken up in 20 mL of a 40% TFA in DCM solution and stirred at 35° C. overnight. The mixture was concentrated in vacuo and passed through a silica plug with 10% MeOH in DCM. Solvent was removed and the residue was dried to give 600 mg crude product as TFA salt for further reactions. LRMS (ESI) m/z 395/397 [(M+H)]+, calc'd for C16H23BrN6O: 395.31.

Workup

  1. customReaction
  2. washwashed with water
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. filtrationfiltered
  5. stirringstirred at 35° C. overnight
  6. concentrationThe mixture was concentrated in vacuo
  7. customSolvent was removed
  8. customthe residue was dried

Sources & evidence

ORD record
ord-0912c57422654433a48f2dd32d83d759
Source dataset
uspto-grants-2015_02
Patent number
US08946415B2

Reaction notes

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