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Sodium Hydroxide → (S)-2-(tert-butoxy)-2-(2-((3,3-dimethylbutyl)carbamoyl)-7-(4,4-dimethylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetic acid

HRID 1630331
ノート
印刷プレビュー

反応式

HRID 1630331 の反応式
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:32])=[N:14][C:15]2[N:16]([N:26]=[C:27]([C:29]([OH:31])=O)[CH:28]=2)[C:17]=1[N:18]1[CH2:23][CH2:22][C:21]([CH3:25])([CH3:24])[CH2:20][CH2:19]1)[C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].[CH3:33][C:34]([CH3:39])([CH3:38])[CH2:35][CH2:36][NH2:37].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[OH-].[Na+]>CN(C=O)C.CN(C1C=CN=CC=1)C.CO.O>[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:32])=[N:14][C:15]2[N:16]([N:26]=[C:27]([C:29](=[O:31])[NH:37][CH2:36][CH2:35][C:34]([CH3:39])([CH3:38])[CH3:33])[CH:28]=2)[C:17]=1[N:18]1[CH2:23][CH2:22][C:21]([CH3:25])([CH3:24])[CH2:20][CH2:19]1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]
参加物実験手順後処理出典と根拠反応ノート

参加物

10

反応物 5

HCID 14798Sodium HydroxideHCID 197093,3-DimethylbutylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 71259137(S)-6-(1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(4,4-dimethylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylic acid

生成物 1

HCID 71259138(S)-2-(tert-butoxy)-2-(2-((3,3-dimethylbutyl)carbamoyl)-7-(4,4-dimethylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetic acid収率 70.5%

試薬・触媒・溶媒 4

HCID 142844-(Dimethylamino)pyridine触媒HCID 887Methanol溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a mixture of (S)-6-(1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(4,4-dimethylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylic acid (50 mg, 0.112 mmol) and 3,3-dimethylbutan-1-amine (22.66 mg, 0.224 mmol) in DMF (2 mL) was added DIEA (0.098 mL, 0.560 mmol), HATU (85 mg, 0.224 mmol) and DMAP (2.74 mg, 0.022 mmol) and the resulting mixture was stirred at room temp for 16 h. At this point LCMS indicated completion of reaction. Water was then added and the mixture was extracted with ethyl acetate (25 mL), washed with brine (15 mL), dried (Na2SO4), filtered and concentrated. Crude was then treated with 1N NaOH (0.336 mL, 0.336 mmol) in MeOH (2.000 mL) at 60° C. for 5 h. Mixture was then cooled and purified by prep-HPLC to afford (S)-2-(tert-butoxy)-2-(2-((3,3-dimethylbutyl)carbamoyl)-7-(4,4-dimethylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetic acid (41.6 mg, 0.079 mmol, 70.4% yield). 1H NMR (500 MHz, DMSO-d6) δ 8.13 (t, J=5.6 Hz, 1H), 6.77 (s, 1H), 5.46 (s, 1H), 3.37-3.28 (m, 6H), 1.92 (s, 3H), 1.67-1.55 (m, 2H), 1.54-1.40 (m, 4H), 1.14 (s, 9H), 1.08 (br. s., 6H), 0.96 (s, 9H). LCMS (M+H)=502.5.

後処理

  1. customcompletion of reaction
  2. extractionthe mixture was extracted with ethyl acetate (25 mL)
  3. washwashed with brine (15 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. temperatureMixture was then cooled
  8. custompurified by prep-HPLC

出典と根拠

ORDレコード
ord-13b5cab2425842e4b24a5bcaaa610b39
出典データセット
uspto-grants-2014_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08791108B2

反応ノート

読み込み中…

このページの内容参加物実験手順後処理出典と根拠反応ノート