Dichloromethane → (2R)-2-({4-[([1,3]Oxathiolo[4,5-c]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dione hydrochloride

HRID 1943212ノート

反応式

HRID 1943212 の反応式
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C@H:9]2[N:19]3[C:20]4[N:11]([C:12](=[O:22])[CH:13]=[CH:14][C:15]=4[N:16]=[CH:17][C:18]3=[O:21])[CH2:10]2)[CH2:4][CH2:3]1.[O:23]1[C:31]2[CH:30]=[C:29]([CH:32]=O)[N:28]=[CH:27][C:26]=2[S:25][CH2:24]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+].[Cl:53]CCl>CO.C(Cl)(Cl)Cl>[ClH:53].[O:23]1[C:31]2[CH:30]=[C:29]([CH2:32][NH:1][CH:2]3[CH2:7][CH2:6][N:5]([CH2:8][C@H:9]4[N:19]5[C:20]6[N:11]([C:12](=[O:22])[CH:13]=[CH:14][C:15]=6[N:16]=[CH:17][C:18]5=[O:21])[CH2:10]4)[CH2:4][CH2:3]3)[N:28]=[CH:27][C:26]=2[S:25][CH2:24]1

参加物

8

反応物 5

HCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 58200877(2R)-2-[(4-Amino-1-piperidinyl)methyl]-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dioneHCID 82413858[1,3]Oxathiolo[4,5-c]pyridine-6-carbaldehyde

生成物 1

HCID 68598289(2R)-2-({4-[([1,3]Oxathiolo[4,5-c]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dione hydrochloride

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6212Chloroform溶媒

実験手順

(2R)-2-[(4-Amino-1-piperidinyl)methyl]-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dione (50 mg, 0.166 mmol) (for a preparation see Example 16(j)) and [1,3]oxathiolo[4,5-c]pyridine-6-carbaldehyde (25 mg, 0.901 eq.) were stirred in 9:1 v:v chloroform:methanol (1 ml) for 2.5 hours. Sodium triacetoxyborohydride (105 mg, 3.000 eq.) was then added in one portion and the mixture was stirred vigorously at room temperature for 30 min. Saturated aqueous sodium hydrogen carbonate (0.5 ML) was then added, followed by dichloromethane (10 ml) and the mixture was stirred vigorously at room temperature for 10 min and the phases were separated (hydrophobic frit). The organic phase was evaporated under reduced pressure and the crude product was purified by column chromatography on silica (eluted with 0-12% (2M NH3 in MeOH) in DCM). Appropriate fractions were combined and evaporated under reduced pressure to give the free base of the title compound as a pale yellow amorphous solid (48 mg).

後処理

  1. stirringthe mixture was stirred vigorously at room temperature for 30 min
  2. stirringthe mixture was stirred vigorously at room temperature for 10 min
  3. customthe phases were separated (hydrophobic frit)
  4. customThe organic phase was evaporated under reduced pressure
  5. customthe crude product was purified by column chromatography on silica (eluted with 0-12% (2M NH3 in MeOH) in DCM)
  6. customevaporated under reduced pressure

出典と根拠

ORDレコード
ord-133ad29f10ea45258c0474232c8a6e9f
出典データセット
uspto-grants-2013_03
特許番号
US08389524B2

反応ノート

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