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Triethylamine → tert-butyl (2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)(6-{[(1-methylcyclopropyl)carbonyl]amino}pyridin-3-yl)carbamate

HRID 1039079
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HRID 1039079 반응식
NC1C(C)=CC([N:8]([CH2:16][CH2:17][C@@H:18]2[CH2:20][C@@H:19]2[CH:21]2[CH2:26][CH2:25][N:24]([C:27]3[N:32]=[CH:31][C:30]([Cl:33])=[CH:29][N:28]=3)[CH2:23][CH2:22]2)[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=NC=1.[CH3:35][C:36]1([C:39]([OH:41])=O)[CH2:38][CH2:37]1.CN(C(O[N:50]1N=N[C:52]2[CH:53]=[CH:54][CH:55]=[N:56][C:51]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C=O)C.C(OCC)(=O)C>[Cl:33][C:30]1[CH:31]=[N:32][C:27]([N:24]2[CH2:23][CH2:22][CH:21]([C@H:19]3[CH2:20][C@H:18]3[CH2:17][CH2:16][N:8]([C:54]3[CH:55]=[N:56][C:51]([NH:50][C:39]([C:36]4([CH3:35])[CH2:38][CH2:37]4)=[O:41])=[CH:52][CH:53]=3)[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH2:26][CH2:25]2)=[N:28][CH:29]=1
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참가 물질

7

반응물 4

HCID 8471TriethylamineHCID 813261-Methylcyclopropanecarboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67962339tert-butyl (5-amino-4-methylpyridin-2-yl)(2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)carbamate

생성물 1

HCID 86666144
tert-butyl (2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)(6-{[(1-methylcyclopropyl)carbonyl]amino}pyridin-3-yl)carbamate

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

tert-butyl (5-amino-4-methylpyridin-2-yl)(2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)carbamate (80 mg, 0.17 mmol) from Step 2 of Example 30a, 1-methylcyclopropane-1-carboxylic acid (19.2 mg, 0.19 mmol), HATU (84 mg, 0.22 mmol) and triethylamine (68.5 mg, 0.68 mmol) were added in DMF (1.7 mL) at room temperature for 2 days. The reaction was added ethyl acetate (20 mL, washed with sodium bicarbonate saturated solution (10 mL), second wash with brine (10 mL). The organic phase was dried by magnesium sulfate, filtered, concentrated and purified by column chromatography through a 25 gram Biotage SNAP KP-Sil™ silica gel cartridge eluting with 30% ethyl acetate/hexanes to give the title compound as a pale yellow oil.

후처리

  1. washwashed with sodium bicarbonate saturated solution (10 mL)
  2. washsecond wash with brine (10 mL)
  3. dry with materialThe organic phase was dried by magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by column chromatography through a 25 gram Biotage SNAP KP-Sil™ silica gel cartridge
  7. washeluting with 30% ethyl acetate/hexanes

출처 및 근거

ORD 기록
ord-64211d634c044e25816265ca9af82ce7
출처 데이터셋
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08552022B2

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