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

HRID 530458

反応式

HRID 530458 の反応式
[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

参加物

9

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

(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]+.

後処理

  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

出典と根拠

ORDレコード
ord-f358402686714a3ebc217aca71bdb2d1
出典データセット
uspto-grants-2016_05
特許番号
US09353086B2

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