(+/-)-2-bromo-4-(5-chloro-2-ethoxycarbonylmethoxy-phenyl)-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid benzyl ester → (+/-)-4-(5-Chloro-2-ethoxycarbonylmethoxy-phenyl)-2-cyclopropyl-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid benzyl ester

HRID 1754842노트

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HRID 1754842 반응식
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][C:14]2[N:17]=[C:18](Br)[S:19][C:13]=2[CH:12]1[C:21]1[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:22]=1[O:28][CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Br-].[CH:36]1([Zn+])[CH2:38][CH2:37]1>C1COCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][C:14]2[N:17]=[C:18]([CH:36]3[CH2:38][CH2:37]3)[S:19][C:13]=2[CH:12]1[C:21]1[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:22]=1[O:28][CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

5

반응물 2

HCID 90022152(+/-)-2-bromo-4-(5-chloro-2-ethoxycarbonylmethoxy-phenyl)-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid benzyl esterHCID 178419765HCID 178419765, 화합물

생성물 1

HCID 118116600(+/-)-4-(5-Chloro-2-ethoxycarbonylmethoxy-phenyl)-2-cyclopropyl-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid benzyl ester

시약·촉매·용매 2

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 8028Tetrahydrofuran용매2회

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온도
50 °C

실험 절차

To a solution under N2 of (±)-2-bromo-4-(5-chloro-2-ethoxycarbonylmethoxy-phenyl)-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid benzyl ester (100 mg, 0.18 mmol, 1.00 eq.) and 0.5M cyclopropylzinc bromide in THF (0.7 mL, 0.35 mmol, 2.00 eq.) in THF (10 mL), tetrakis(triphenylphosphine) palladium (0) (10.2 mg, 9 μmol was added. The mixture was stirred at 50° C. for 18 hours. The mixture was allowed to cool to r.t. and concentrated in vacuo. The residue was diluted with DCM (50 mL) and washed with water (2×25 mL). The org. layer was dried over MgSO4 and concentrated in vacuo. The residue was taken up in DMF, filtered, and then purified by prep. HPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo to give the title compound.

후처리

  1. temperatureto cool to r.t.
  2. concentrationconcentrated in vacuo
  3. additionThe residue was diluted with DCM (50 mL)
  4. washwashed with water (2×25 mL)
  5. dry with materiallayer was dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. filtrationfiltered
  8. custompurified by prep
  9. concentrationHPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo

출처 및 근거

ORD 기록
ord-57607cbcbf2749e6811ebc29129bde66
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09169270B2

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