Diisopropylethylamine → 4-[[4-(dimethylamIno)cyclohexyl]oxy]-6-ethyl-N-(3-fluoropyridin-4-yl)thieno[2,3-d]pyrimidine-5-carboxamide

HRID 2369406

Reaktionsgleichung

Reaktionsgleichung von HRID 2369406
[CH3:1][N:2]([CH3:24])[CH:3]1[CH2:8][CH2:7][CH:6]([O:9][C:10]2[C:11]3[C:18]([C:19](O)=[O:20])=[C:17]([CH2:22][CH3:23])[S:16][C:12]=3[N:13]=[CH:14][N:15]=2)[CH2:5][CH2:4]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[F:58][C:59]1[CH:60]=[N:61][CH:62]=[CH:63][C:64]=1[NH2:65]>CN(C=O)C>[CH3:24][N:2]([CH3:1])[CH:3]1[CH2:8][CH2:7][CH:6]([O:9][C:10]2[C:11]3[C:18]([C:19]([NH:65][C:64]4[CH:63]=[CH:62][N:61]=[CH:60][C:59]=4[F:58])=[O:20])=[C:17]([CH2:22][CH3:23])[S:16][C:12]=3[N:13]=[CH:14][N:15]=2)[CH2:5][CH2:4]1

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 8171224-Amino-3-fluoropyridineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 681099564-[[4-(Dimethylamino)cyclohexyl]oxy]-6-ethylthieno[2,3-d]pyrimidine-5-carboxylic acid

Produkt 1

HCID 681101714-[[4-(dimethylamIno)cyclohexyl]oxy]-6-ethyl-N-(3-fluoropyridin-4-yl)thieno[2,3-d]pyrimidine-5-carboxamideAusbeute 31,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of 4-[[4-(dimethylamino)cyclohexyl]oxy]-6-ethylthieno[2,3-d]pyrimidine-5-carboxylic acid (100 mg, 0.29 mmol, 1.00 equiv) in distilled DMF (5 mL) was added HATU (217 mg, 0.57 mmol, 2.00 equiv), DIEA (110.9 mg, 0.86 mmol, 3.00 equiv) and 3-fluoropyridin-4-amine (32 mg, 0.29 mmol, 1.00 equiv) under nitrogen. The resulting solution was stirred for 1 h at room temperature. After evaporation under reduced pressure, the crude product (120 mg) was purified by Prep-HPLC with the following conditions (Waters): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, water with 0.05% NH4HCO3 and CH3CN (7.0% CH3CN up to 48.0% in 10 min); Flow rate, 20 mL/min; UV detection at 254/220 nm. The product-containing fractions were collected and partially evaporated to remove water and CH3CN under reduced pressure. The residue was lyophilized overnight to give the corresponding 4-[[4-(dimethylamino)cyclohexyl]oxy]-6-ethyl-N-(3-fluoropyridin-4-yl)thieno[2,3-d]pyrimidine-5-carboxamide (40 mg) as a white solid. MS (ES, m/z): 444 [M+H]+. 1H NMR: (400 MHz, CD3OD): 8.55-8.59 (2H, m), 8.50 (1H, d), 8.40 (1H, d), 5.19-5.24 (1H, m), 3.07 (2H, q), 2.28 (6H, s), 2.10-2.19 (3H, m), 1.89-1.92 (2H, m), 1.27-1.43 (5H, m), 1.22-1.25 (2H, m).

Aufarbeitung

  1. customAfter evaporation under reduced pressure
  2. customthe crude product (120 mg) was purified by Prep-HPLC with the following conditions (Waters)
  3. waitmobile phase, water with 0.05% NH4HCO3 and CH3CN (7.0% CH3CN up to 48.0% in 10 min)
  4. customThe product-containing fractions were collected
  5. custompartially evaporated
  6. customto remove water and CH3CN under reduced pressure
  7. waitThe residue was lyophilized overnight

Quellen und Nachweise

ORD-Eintrag
ord-a857516f098a4c489e0f16591a26ea30
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08703941B2

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