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Triethylamine → (9-(3-Fluoro-5-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-5-yl)methanone

HRID 471109
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HRID 471109 반응식
[O:1]1[C:6]2([CH2:11][CH2:10][N:9]([CH2:12][C:13]3[CH:14]=[C:15]([CH2:20][CH2:21][OH:22])[CH:16]=[C:17]([F:19])[CH:18]=3)[CH2:8][CH2:7]2)[CH2:5][NH:4][CH2:3][CH2:2]1.C(N(CC)CC)C.[CH:30]([C:33]1[S:34][C:35]([C:38](O)=[O:39])=[CH:36][N:37]=1)([CH3:32])[CH3:31].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[F:19][C:17]1[CH:18]=[C:13]([CH:14]=[C:15]([CH2:20][CH2:21][OH:22])[CH:16]=1)[CH2:12][N:9]1[CH2:10][CH2:11][C:6]2([O:1][CH2:2][CH2:3][N:4]([C:38]([C:35]3[S:34][C:33]([CH:30]([CH3:32])[CH3:31])=[N:37][CH:36]=3)=[O:39])[CH2:5]2)[CH2:7][CH2:8]1
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6

반응물 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 197863422-(Propan-2-yl)-1,3-thiazole-5-carboxylic acidHCID 579889902-(3-(1-Oxa-4,9-diazaspiro[5.5]undecan-9-ylmethyl)-5-fluorophenyl)ethanol

생성물 1

HCID 57988964
(9-(3-Fluoro-5-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-5-yl)methanone

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
0 °C

실험 절차

A solution of 2-(3-(1-oxa-4,9-diazaspiro[5.5]undecan-9-ylmethyl)-5-fluorophenyl)ethanol (example 55, step c) (0.153 g) in DMF (7 mL) was treated with triethylamine (0.208 mL) followed by 2-isopropylthiazole-5-carboxylic acid (example 55, step b) (0.085 g). The mixture was cooled to 0° C. and HATU (0.245 g) was added. The reaction mixture was stirred for 2 hours at 20° C. The mixture was partitioned between ethyl acetate and brine, the organic layer was washed twice with brine, dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure. The crude product was purified by flash silica chromatography using 2.5% methanol in dichloromethane with 1% triethylamine as solvent. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 0.130 g.

후처리

  1. customThe mixture was partitioned between ethyl acetate and brine
  2. washthe organic layer was washed twice with brine
  3. dry with materialdried over sodium sulphate
  4. filtrationfiltered
  5. customthe solvent evaporated under reduced pressure
  6. customThe crude product was purified by flash silica chromatography
  7. customPure fractions were evaporated to dryness

출처 및 근거

ORD 기록
ord-539c8f22f1174dfa9d5b2d055b03c322
출처 데이터셋
uspto-grants-2014_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08629271B2

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