Sodium Bicarbonate → (4S)-3,8-Difluoro-4-hydroxy-4-({4-[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one dihydrochloride

HRID 15141

반응식

HRID 15141 반응식
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C@@:9]2([OH:24])[C:13]3=[C:14]([F:23])[CH:15]=[N:16][C:17]4[CH:18]=[C:19]([F:22])[C:20](=[O:21])[N:11]([C:12]=43)[CH2:10]2)[CH2:4][CH2:3]1.[S:25]1[C:33]2[CH:32]=[C:31]([CH:34]=O)[N:30]=[CH:29][C:28]=2[O:27][CH2:26]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+].C(Cl)(Cl)[Cl:56].CO>>[ClH:56].[ClH:56].[F:23][C:14]1[CH:15]=[N:16][C:17]2[CH:18]=[C:19]([F:22])[C:20](=[O:21])[N:11]3[CH2:10][C@@:9]([OH:24])([CH2:8][N:5]4[CH2:4][CH2:3][CH:2]([NH:1][CH2:34][C:31]5[N:30]=[CH:29][C:28]6[O:27][CH2:26][S:25][C:33]=6[CH:32]=5)[CH2:7][CH2:6]4)[C:13]=1[C:12]=23

참가 물질

6

반응물 5

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 21584188Chloroform methanolHCID 23633410(4S)-4-[(4-amino-1-piperidinyl)methyl]-3,8-difluoro-4-hydroxy-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-oneHCID 59254367[1,3]Oxathiolo[5,4-c]pyridine-6-carbaldehyde

생성물 1

HCID 67527143(4S)-3,8-Difluoro-4-hydroxy-4-({4-[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one dihydrochloride수율 36%

실험 절차

A solution of (4S)-4-[(4-amino-1-piperidinyl)methyl]-3,8-difluoro-4-hydroxy-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one (E1 enantiomer) (180 mg, 0.536 mmol) and [1,3]oxathiolo[5,4-c]pyridine-6-carbaldehyde (89 mg, 0.536 mmol) (for a synthesis, see WO2004058144, Example 61) in chloroform/methanol (5 ml/0.5 ml) was stirred at room temperature under argon for 1 h before treatment with sodium triacetoxyborohydride (341 mg, 1.608 mmol). After 1 h stirring the reaction mixture was treated with saturated sodium bicarbonate (20 ml). The aqueous layer was extracted with a 10% solution of methanol in dichloromethane (3×200 ml). The combined organic extracts were dried over magnesium sulphate and evaporated. The residue was chromatographed eluting with a 0-20% gradient of methanol in dichloromethane to yield 82 mg initially and 13 mg by re-chromatographing mixed fractions of the free base of the title compound as a yellow solid (95 mg, 36%).

후처리

  1. extractionThe aqueous layer was extracted with a 10% solution of methanol in dichloromethane (3×200 ml)
  2. dry with materialThe combined organic extracts were dried over magnesium sulphate
  3. customevaporated
  4. customThe residue was chromatographed
  5. washeluting with a 0-20% gradient of methanol in dichloromethane
  6. customto yield 82 mg initially

출처 및 근거

ORD 기록
ord-5de9674b51d842ddac95d666537da970
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07732460B2

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