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

HRID 471150ノート

反応式

HRID 471150 の反応式
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:25]([C:28]1[S:32][CH:31]=[C:30]([C:33]([OH:35])=O)[CH:29]=1)([CH3:27])[CH3:26].[O:36]1[C:41]2([CH2:46][CH2:45][N:44]([CH2:47][C:48]3[C:49]([F:57])=[C:50]([CH2:54][CH2:55][OH:56])[CH:51]=[CH:52][CH:53]=3)[CH2:43][CH2:42]2)[CH2:40][NH:39][CH2:38][CH2:37]1.C(N(CC)CC)C>CN(C=O)C>[F:57][C:49]1[C:50]([CH2:54][CH2:55][OH:56])=[CH:51][CH:52]=[CH:53][C:48]=1[CH2:47][N:44]1[CH2:45][CH2:46][C:41]2([O:36][CH2:37][CH2:38][N:39]([C:33]([C:30]3[CH:29]=[C:28]([CH:25]([CH3:26])[CH3:27])[S:32][CH:31]=3)=[O:35])[CH2:40]2)[CH2:42][CH2:43]1

参加物

6

反応物 4

HCID 8471TriethylamineHCID 35250805-Isopropylthiophene-3-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 579891872-(3-(1-Oxa-4,9-diazaspiro[5.5]undecan-9-ylmethyl)-2-fluorophenyl)ethanol

生成物 1

HCID 57989041(9-(2-Fluoro-3-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(5-isopropylthiophen-3-yl)methanone

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

HATU (0.183 g) was added in one portion to a stirred solution at 0° C. of 5-isopropylthiophene-3-carboxylic acid (0.063 g) and 2-(3-(1-oxa-4,9-diazaspiro[5.5]undecan-9-ylmethyl)-2-fluorophenyl)ethanol (example 67, step f) (0.114 g) and triethylamine (0.155 mL) in DMF (5 mL). The reaction mixture was stirred at room temperature for 2 hours. 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 0.100 g.

後処理

  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

出典と根拠

ORDレコード
ord-b8939b2324994f0baa0593cba3927cc2
出典データセット
uspto-grants-2014_01
特許番号
US08629271B2

反応ノート

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