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5-Tert-butylthiophene-2-carboxylic acid → (S)-tert-butyl 1-((S)-2-(5-(tert-butyl)thiophene-2-carboxamido)-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl) propanoyl)pyrrolidine-2-carboxylate

HRID 1775857
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1775857
[NH2:1][C@@H:2]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[N:29]=[CH:28][C:27]([C:30]3[CH:35]=[CH:34][C:33]([O:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43])=[CH:32][CH:31]=3)=[CH:26][N:25]=2)=[CH:20][CH:19]=1)[C:3]([N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])=[O:4].[C:44]([C:48]1[S:52][C:51]([C:53](O)=[O:54])=[CH:50][CH:49]=1)([CH3:47])([CH3:46])[CH3:45].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CC(=O)OCC>[C:44]([C:48]1[S:52][C:51]([C:53]([NH:1][C@@H:2]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[N:29]=[CH:28][C:27]([C:30]4[CH:35]=[CH:34][C:33]([O:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43])=[CH:32][CH:31]=4)=[CH:26][N:25]=3)=[CH:20][CH:19]=2)[C:3]([N:5]2[CH2:9][CH2:8][CH2:7][C@H:6]2[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])=[O:4])=[O:54])=[CH:50][CH:49]=1)([CH3:47])([CH3:45])[CH3:46]
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Komponenten

6

Edukt 3

HCID 4583495-Tert-butylthiophene-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 117741043(S)-tert-butyl 1-((S)-2-amino-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)propanoyl)pyrrolidine-2-carboxylate

Produkt 1

HCID 117740760
(S)-tert-butyl 1-((S)-2-(5-(tert-butyl)thiophene-2-carboxamido)-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl) propanoyl)pyrrolidine-2-carboxylate
Ausbeute 92,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Prepared using General Procedure 7: A stirred solution of (S)-tert-butyl 1-((S)-2-amino-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)propanoyl)pyrrolidine-2-carboxylate (306 mg, 0.522 mmol) and 5-(tert-butyl)thiophene-2-carboxylic acid (106 mg, 0.574 mmol) in DMF (6 mL) was added TEA (145 μl, 1.043 mmol), cooled to 0° C., then HATU (218 mg, 0.574 mmol) was slowly added over 5 minutes. The reaction was stirred at room temperature for 2 h, then diluted with EA (70 mL), washed with saturated aqueous NaHCO3 (70 mL) and brine (100 mL). The solvent was dried over MgSO4 and removed. The crude product was purified by chromatography 0-30% ACN in DCM to afford 363 mg (92%) of (S)-tert-butyl 1-((S)-2-(5-(tert-butyl)thiophene-2-carboxamido)-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl) propanoyl)pyrrolidine-2-carboxylate as a sticky solid. LCMS-ESI (m/z) calculated for C44H56N4O5S: 752.4; no m/z observed, tR=11.99 min (Method 10).

Aufarbeitung

  1. customPrepared
  2. washwashed with saturated aqueous NaHCO3 (70 mL) and brine (100 mL)
  3. dry with materialThe solvent was dried over MgSO4
  4. customremoved
  5. customThe crude product was purified by chromatography 0-30% ACN in DCM

Quellen und Nachweise

ORD-Eintrag
ord-d68a9bf9145b4868be90bf2b4130d6fa
Quelldatensatz
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09260427B2

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