Diisopropylethylamine → 4-(Tetrahydro-pyran-4-carbonyl)-[1,4]diazepane-1-carboxylic acid (5-tert-butyl-4-methyl-thiazol-2-yl)-amide

HRID 1920724ノート

反応式

HRID 1920724 の反応式
[C:1]([C:5]1[S:9][C:8]([NH2:10])=[N:7][C:6]=1[CH3:11])([CH3:4])([CH3:3])[CH3:2].Cl[C:13](OCC(Cl)(Cl)Cl)=[O:14].C(N(CC)C(C)C)(C)C.[N:30]1([C:37]([CH:39]2[CH2:44][CH2:43][O:42][CH2:41][CH2:40]2)=[O:38])[CH2:36][CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1>C(Cl)Cl.ClCCCl>[C:1]([C:5]1[S:9][C:8]([NH:10][C:13]([N:33]2[CH2:34][CH2:35][CH2:36][N:30]([C:37]([CH:39]3[CH2:44][CH2:43][O:42][CH2:41][CH2:40]3)=[O:38])[CH2:31][CH2:32]2)=[O:14])=[N:7][C:6]=1[CH3:11])([CH3:4])([CH3:3])[CH3:2]

参加物

7

反応物 4

HCID 81531Diisopropylethylamine2 回HCID 870632,2,2-Trichloroethyl chloroformateHCID 10815365-tert-Butyl-4-methyl-thiazol-2-ylamineHCID 28776660(1,4-Diazepan-1-yl)(tetrahydro-2H-pyran-4-yl)methanone

生成物 1

HCID 591433724-(Tetrahydro-pyran-4-carbonyl)-[1,4]diazepane-1-carboxylic acid (5-tert-butyl-4-methyl-thiazol-2-yl)-amide収率 28.4%

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 6344Dichloromethane溶媒

実験手順

To a solution of 137.8 mg (0.8 mmol) of 5-tert-butyl-4-methyl-thiazol-2-ylamine in DCM (4 mL) were added 169.5 mg (0.8 mmol) of 2,2,2-trichloroethyl chloroformate and 0.21 mL (1.2 mmol) of N,N-diisopropylethylamine. The reaction was stirred for 18 h at room temperature. The reaction mixture was washed with saturated aqueous NaHCO3 solution and the aqueous layer was back-extracted with DCM (2×2 mL). The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The residue was dissolved in DCE (4 mL) and a solution of 443 mg (0.8 mmol) of [1,4]diazepan-1-yl-(tetrahydro-pyran-4-yl)-methanone (triple trifluoroacetic acid salt, prepared according to Method L, step 1-2) in DCE (2 mL) and 0.42 mL (2.4 mmol) of N,N-diisopropylethylamine were added. The reaction was stirred for 18 h at 80° C. The reaction mixture was washed with 10% aqueous citric acid solution (3 mL). The aqueous layer was back-extracted with DCM (2×2 mL). The combined organic extracts were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified by mass-triggered preparative LCMS to afford 92.7 mg of 4-(tetrahydro-pyran-4-carbonyl)-[1,4]diazepane-1-carboxylic acid (5-tert-butyl-4-methyl-thiazol-2-yl)-amide.

後処理

  1. washThe reaction mixture was washed with saturated aqueous NaHCO3 solution
  2. extractionthe aqueous layer was back-extracted with DCM (2×2 mL)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. dissolutionThe residue was dissolved in DCE (4 mL)
  7. stirringThe reaction was stirred for 18 h at 80° C
  8. washThe reaction mixture was washed with 10% aqueous citric acid solution (3 mL)
  9. extractionThe aqueous layer was back-extracted with DCM (2×2 mL)
  10. dry with materialThe combined organic extracts were dried over Na2SO4
  11. filtrationfiltered
  12. concentrationthe filtrate was concentrated under reduced pressure
  13. customThe crude product was purified by mass-triggered preparative LCMS

出典と根拠

ORDレコード
ord-81454685b10a44d8bee92f086eff9f88
出典データセット
uspto-grants-2012_05
特許番号
US08173638B2

反応ノート

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