Formaldehyde → tert-Butyl 3-[(4-benzyl-1,4-diazepan-1-yl)carbonyl]-4-methylpiperazine-1-carboxylate

HRID 530458

Reaktionsgleichung

Reaktionsgleichung von HRID 530458
[C:1]([N:8]1[CH2:13][CH2:12][NH:11][C@H:10]([C:14]([OH:16])=O)[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C=O.[BH-](OC(C)=O)(OC(C)=O)O[C:21](C)=O.[Na+].[CH2:33]([N:40]1[CH2:46][CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CO.CN(C=O)C>[CH2:33]([N:40]1[CH2:46][CH2:45][CH2:44][N:43]([C:14]([CH:10]2[N:11]([CH3:21])[CH2:12][CH2:13][N:8]([C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[CH2:9]2)=[O:16])[CH2:42][CH2:41]1)[C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1

Komponenten

9

Edukt 6

HCID 712FormaldehydeHCID 81531DiisopropylethylamineHCID 2283651-Benzyl-1,4-diazepaneHCID 1501850(S)-4-N-Boc-piperazine-2-carboxylic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 5049666Sodium triacetoxyborohydride

Produkt 1

HCID 86700709tert-Butyl 3-[(4-benzyl-1,4-diazepan-1-yl)carbonyl]-4-methylpiperazine-1-carboxylateAusbeute 71 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

(S)-4-Boc-2-piperazinecarboxylic acid (530 mg, 2.17 mmol) was dissolved in MeOH (25 mL) and formaldehyde (1.76 mL, 37 wt % in water, 21.7 mmol) was added. The reaction mixture was stirred for 30 min, NaBH(OAc)3 (0.92 g, 4.34 mmol) was added and the reaction mixture was stirred for 2 h. The solvents were removed in vacuo and the residue was purified by reverse phase column chromatography. The residue and benzyl homopiperazine (0.41 g, 2.17 mmol) were dissolved in DMF (20 mL) and cooled to 0° C. DIPEA (0.59 g, 4.56 mmol) and HBTU (0.82 g, 2.17 mmol) were added and the reaction mixture was stirred for 3 h. The solvents were removed in vacuo and the residue was partitioned between DCM (100 mL) and water (50 mL). The organic fraction was washed with 1M aq Na2CO3 (25 mL), brine (25 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by reverse phase column chromatography to give the title compound (0.64 g, 71%) as a light yellow gum. LCMS (ES+): 417.4 [MH]+.

Aufarbeitung

  1. stirringthe reaction mixture was stirred for 2 h
  2. customThe solvents were removed in vacuo
  3. customthe residue was purified by reverse phase column chromatography
  4. stirringthe reaction mixture was stirred for 3 h
  5. customThe solvents were removed in vacuo
  6. customthe residue was partitioned between DCM (100 mL) and water (50 mL)
  7. washThe organic fraction was washed with 1M aq Na2CO3 (25 mL), brine (25 mL)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by reverse phase column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-f358402686714a3ebc217aca71bdb2d1
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09353086B2

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