Sodium Hydroxide → (S,E)-2-(tert-butoxy)-2-(2-((3,3-dimethylbutyl)carbamoyl)-5-methyl-7-(4-methylpent-1-en-1-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetic acid

HRID 1630327노트

반응식

HRID 1630327 반응식
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:30])=[N:14][C:15]2[N:16]([N:24]=[C:25]([C:27](O)=[O:28])[CH:26]=2)[C:17]=1/[CH:18]=[CH:19]/[CH2:20][CH:21]([CH3:23])[CH3:22])[C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].[CH3:31][C:32]([CH3:37])([CH3:36])[CH2:33][CH2:34][NH2:35].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]([CH3:30])=[N:14][C:15]2[N:16]([N:24]=[C:25]([C:27](=[O:28])[NH:35][CH2:34][CH2:33][C:32]([CH3:37])([CH3:36])[CH3:31])[CH:26]=2)[C:17]=1/[CH:18]=[CH:19]/[CH2:20][CH:21]([CH3:23])[CH3:22])[C:7]([OH:9])=[O:8])([CH3:2])([CH3:3])[CH3:4]

참가 물질

10

반응물 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 71259118(S,E)-6-(1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-5-methyl-7-(4-methylpent-1-en-1-yl)pyrazolo[1,5-a]pyrimidine-2-carboxylic acid

생성물 1

HCID 71258328(S,E)-2-(tert-butoxy)-2-(2-((3,3-dimethylbutyl)carbamoyl)-5-methyl-7-(4-methylpent-1-en-1-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetic acid수율 10.35%

시약·촉매·용매 4

HCID 142844-(Dimethylamino)pyridine촉매HCID 887Methanol용매HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

To a mixture of (S,E)-6-(1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-5-methyl-7-(4-methylpent-1-en-1-yl)pyrazolo[1,5-a]pyrimidine-2-carboxylic acid (30 mg, 0.072 mmol) and 3,3-dimethylbutan-1-amine (14.54 mg, 0.144 mmol) in DMF (1.5 mL) was added DIEA (0.063 mL, 0.359 mmol), HATU (54.6 mg, 0.144 mmol) and DMAP (1.756 mg, 0.014 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 ether (25 mL), washed with brine (15 mL), dried (Na2SO4), filtered and concentrated. Crude was then treated with 1N NaOH (0.216 mL, 0.216 mmol) in MeOH (1.500 mL) at 60° C. for 5 h. Mixture was then cooled and purified by prep-HPLC to afford (S,E)-2-(tert-butoxy)-2-(2-((3,3-dimethylbutyl)carbamoyl)-5-methyl-7-(4-methylpent-1-en-1-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetic acid (3.7 mg, 7.44 μmol, 10.35% yield). 1H NMR (500 MHz, DMSO-d6) δ 8.29 (t, J=6.0 Hz, 1H), 7.05 (d, J=14.0 Hz, 1H), 6.88 (s, 1H), 5.38 (s, 1H), 3.36-3.29 (m, 2H), 2.62 (s, 3H), 2.40-2.27 (m, 2H), 1.86 (dt, J=13.2, 6.7 Hz, 1H), 1.52-1.44 (m, 2H), 1.08 (s, 9H), 1.00 (d, J=3.7 Hz, 3H), 1.02 (d, J=3.7 Hz, 3H), 0.95 (s, 19H). LCMS (M+H)=473.4.

후처리

  1. customcompletion of reaction
  2. extractionthe mixture was extracted with ether (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

출처 및 근거

ORD 기록
ord-7765f8663aa443fb965eaea3a0dd0051
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08791108B2

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