Diisopropylethylamine → HCID 57955617, Verbindung

HRID 914241Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 914241
[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:33][CH:34]1[CH2:37][N:36]([CH:38]2[CH2:43][CH2:42][N:41](C(OC(C)(C)C)=O)[CH2:40][CH2:39]2)[CH2:35]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>CN(C=O)C.O>[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26]([NH:33][CH:34]5[CH2:35][N:36]([CH:38]6[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]6)[CH2:37]5)=[O:27])=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 252529054-(9-Cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acidHCID 45072277Tert-butyl 4-(3-aminoazetidin-1-YL)piperidine-1-carboxylate

Produkt 1

HCID 57955617HCID 57955617, VerbindungAusbeute 14 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid (100 mg, 0.22 mmol) in DMF (1 mL) was added tert-butyl 4-(3-aminoazetidin-1-yl)piperidine-1-carboxylate (72 mg, 0.25 mmol), HATU (125 mg, 0.33 mmol), and DIEA (80 μL, 0.44 mmol). The reaction mixture was stirred for 1 h. It was then poured into 100 mL of rapidly stirring water. A white solid forms and was filtered, washed with water and dried. This solid was treated with TFA in DCM (3 mL 1:1) for 2 days. The solvent was then removed, and the product purified by reverse phase HPLC, free based and lyophilized to yield a white solid (17.8 mg, 14% yield 1H NMR (400 MHz, DMSO-d6) δ ppm 1.02 (br. s., 2H) 1.50-1.79 (m, 9H) 1.93 (br. s., 2H) 2.07 (br. s., 1H) 2.35-2.44 (m, 2H) 2.85-3.00 (m, 4H) 3.52 (t, J=7.20 Hz, 2H) 3.94 (s, 3H) 4.05 (t, J=14.02 Hz, 2H) 4.37-4.50 (m, 1H) 4.68-4.84 (m, 1H) 7.47-7.52 (m, 2H) 7.98 (s, 1H) 8.26 (s, 1H) 8.29 (d, 1H) 8.61 (d, J=6.57 Hz, 1H). [M+H] calc'd for C29H38F2N8O3, 585. found 585.

Aufarbeitung

  1. filtrationA white solid forms and was filtered
  2. washwashed with water
  3. customdried
  4. additionThis solid was treated with TFA in DCM (3 mL 1:1) for 2 days
  5. customThe solvent was then removed
  6. customthe product purified by reverse phase HPLC
  7. customto yield a white solid (17.8 mg, 14% yield 1H NMR (400 MHz, DMSO-d6) δ ppm 1.02 (br. s., 2H) 1.50-1.79 (m, 9H) 1.93 (br. s., 2H) 2.07 (br. s., 1H) 2.35-2.44 (m, 2H) 2.85-3.00 (m, 4H) 3.52 (t, J=7.20 Hz, 2H) 3.94 (s, 3H) 4.05 (t, J=14.02 Hz, 2H) 4.37-4.50 (m, 1H) 4.68-4.84 (m, 1H) 7.47-7.52 (m, 2H) 7.98 (s, 1H) 8.26 (s, 1H) 8.29 (d, 1H) 8.61 (d, J=6.57 Hz, 1H)

Quellen und Nachweise

ORD-Eintrag
ord-d27ab7336032476ba6b4ebd5c9029ce6
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08026234B2

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