Chloroform → (1R)-1-({4-Methyl-4-[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione hydrochloride

HRID 1943208ノート

反応式

HRID 1943208 の反応式
[NH2:1][C:2]1([CH3:23])[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[CH:16]=[CH:17][C:18]3=[O:21])[CH2:10]2)[CH2:4][CH2:3]1.[S:24]1[C:32]2[CH:31]=[C:30]([CH:33]=O)[N:29]=[CH:28][C:27]=2[O:26][CH2:25]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+].C(Cl)(Cl)[Cl:55]>CO>[ClH:55].[CH3:23][C:2]1([NH:1][CH2:33][C:30]2[N:29]=[CH:28][C:27]3[O:26][CH2:25][S:24][C:32]=3[CH:31]=2)[CH2:3][CH2:4][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[CH:16]=[CH:17][C:18]3=[O:21])[CH2:10]2)[CH2:6][CH2:7]1

参加物

7

反応物 5

HCID 6212ChloroformHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 59254367[1,3]Oxathiolo[5,4-c]pyridine-6-carbaldehydeHCID 68595973(1R)-1-[(4-Amino-4-methyl-1-piperidinyl)methyl]-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione

生成物 1

HCID 68598707(1R)-1-({4-Methyl-4-[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione hydrochloride収率 75%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

A suspension of (1R)-1-[(4-amino-4-methyl-1-piperidinyl)methyl]-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione (26 mg, 0.083 mmol) (for a preparation see Example 23(i)) in chloroform (2 ml) and methanol (0.1 ml) at rt under argon was treated with [1,3]oxathiolo[5,4-c]pyridine-6-carbaldehyde (13.83 mg, 0.083 mmol) (for a synthesis see WO2004058144 Example 61) and stirred at rt for 2 h. The solution was then treated with sodium triacetoxyborohydride (52.6 mg, 0.248 mmol) and stirred at rt for 0.5 h. The reaction was then treated with saturated aqueous NaHCO3 (10 ml) and extracted with 20% methanol/DCM (3×50 ml). The combined organic fractions were dried (MgSO4), filtered, evaporated and chromatographed (0-20% methanol/DCM, Rf=0.3 in 15% methanol/DCM) to give the free base of the title compound as a yellow solid (29 mg, 75%,).

後処理

  1. stirringstirred at rt for 0.5 h
  2. extractionextracted with 20% methanol/DCM (3×50 ml)
  3. dry with materialThe combined organic fractions were dried (MgSO4)
  4. filtrationfiltered
  5. customevaporated
  6. customchromatographed (0-20% methanol/DCM, Rf=0.3 in 15% methanol/DCM)

出典と根拠

ORDレコード
ord-2f486dc0d6e44af7a3c985616ddfef6d
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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