Triethylamine → cis-N-(3-{4-[4-(Octahydro-quinoline-1-carbonyl)-thiophen-2-yl]-piperidin-1-yl}-3-oxo-propyl)-methanesulfonamide

HRID 1809071ノート

反応式

HRID 1809071 の反応式
[N:1]1([C:11]([C:13]2[CH:17]=[C:16]([CH:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)[S:15][CH:14]=2)=[O:12])[C@@H:10]2[C@@H:5]([CH2:6][CH2:7][CH2:8][CH2:9]2)[CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(OC([NH:62][CH2:63][CH2:64][C:65]([OH:67])=O)=O)(C)(C)C.[CH3:68][S:69](Cl)(=[O:71])=[O:70]>C(#N)C.O.C(Cl)Cl>[N:1]1([C:11]([C:13]2[CH:17]=[C:16]([CH:18]3[CH2:19][CH2:20][N:21]([C:65](=[O:67])[CH2:64][CH2:63][NH:62][S:69]([CH3:68])(=[O:71])=[O:70])[CH2:22][CH2:23]3)[S:15][CH:14]=2)=[O:12])[C@@H:10]2[C@@H:5]([CH2:6][CH2:7][CH2:8][CH2:9]2)[CH2:4][CH2:3][CH2:2]1

参加物

9

反応物 5

HCID 8471Triethylamine2 回HCID 31297Methanesulfonyl chlorideHCID 76809N-((1,1-dimethylethoxy)carbonyl)-beta-alanineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86646702cis-(Octahydro-quinolin-1-yl)-(5-piperidin-4-yl-thiophen-3-yl)-methanone

生成物 1

HCID 86646707cis-N-(3-{4-[4-(Octahydro-quinoline-1-carbonyl)-thiophen-2-yl]-piperidin-1-yl}-3-oxo-propyl)-methanesulfonamide収率 48.8%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒

実験手順

To a solution of cis-(octahydro-quinolin-1-yl)-(5-piperidin-4-yl-thiophen-3-yl)-methanone (CC-033) (0.065 g, 0.20 mmol) in acetonitrile (1 mL) was added triethylamine (0.59 mmol), HATU (0.22 mmol) and N-t-butyloxycarbonyl β-alanine (0.22 mmol). The reaction mixture was stirred for 4 hours, and then the solvent was removed by evaporation. The residue was dissolved in TFA (2 mL) and DCM (2 mL) and the reaction mixture stirred for 2 hours. The solvent was evaporated and the residue purified by flash chromatography on an SCX-2 cartridge, eluting with acetonitrile and then 2 M ammonia in methanol. The fractions containing 3-amino-1-{4-[4-(octahydro-quinoline-1-carbonyl)-thiophen-2-yl]-piperidin-1-yl}-propan-1-one were concentrated under vacuum to a colourless oil (0.089 g). The oil was dissolved in DCM (1 mL) and triethylamine (0.33 mmol) and methanesulphonyl chloride (0.22 mmol) were added. The mixture was stirred for 18 hours and then diluted with water and DCM. The organic solution was separated, dried and the solvent evaporated. The residue was purified by HPLC, eluting with 10%-98% acetonitrile in water (0.1% formic acid). The fractions containing the desired product were concentrated under vacuum to give the title compound as a colourless oil (0.047 g). LCMS mk 482.09 [M+H]+ RT=9.52 min (Analytical Method 2).

後処理

  1. customthe solvent was removed by evaporation
  2. dissolutionThe residue was dissolved in TFA (2 mL)
  3. stirringDCM (2 mL) and the reaction mixture stirred for 2 hours
  4. customThe solvent was evaporated
  5. customthe residue purified by flash chromatography on an SCX-2 cartridge
  6. washeluting with acetonitrile
  7. additionThe fractions containing 3-amino-1-{4-[4-(octahydro-quinoline-1-carbonyl)-thiophen-2-yl]-piperidin-1-yl}-propan-1-one
  8. concentrationwere concentrated under vacuum to a colourless oil (0.089 g)
  9. dissolutionThe oil was dissolved in DCM (1 mL)
  10. stirringThe mixture was stirred for 18 hours
  11. customThe organic solution was separated
  12. customdried
  13. customthe solvent evaporated
  14. customThe residue was purified by HPLC
  15. washeluting with 10%-98% acetonitrile in water (0.1% formic acid)
  16. additionThe fractions containing the desired product
  17. concentrationwere concentrated under vacuum

出典と根拠

ORDレコード
ord-4d009d524f484243a6830098b2669239
出典データセット
uspto-grants-2013_01
特許番号
US08362008B2

反応ノート

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