Triethylamine → HCID 56666620, Verbindung

HRID 1040911Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1040911
[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9]1[C:14]([Cl:15])=[CH:13][N:12]=[C:11]([NH:16][C:17]2[CH:31]=[CH:30][C:20]3[CH2:21][CH2:22][N:23]([CH2:26][CH2:27][O:28][CH3:29])[CH2:24][CH2:25][C:19]=3[CH:18]=2)[N:10]=1.C(N(CC)CC)C.[F:39][C:40]([F:47])([F:46])[CH2:41][S:42](Cl)(=[O:44])=[O:43]>C(Cl)Cl>[Cl:15][C:14]1[C:9]([NH:8][C@@H:3]2[CH2:4][CH2:5][CH2:6][CH2:7][C@H:2]2[NH:1][S:42]([CH2:41][C:40]([F:47])([F:46])[F:39])(=[O:44])=[O:43])=[N:10][C:11]([NH:16][C:17]2[CH:31]=[CH:30][C:20]3[CH2:21][CH2:22][N:23]([CH2:26][CH2:27][O:28][CH3:29])[CH2:24][CH2:25][C:19]=3[CH:18]=2)=[N:12][CH:13]=1

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 742422,2,2-Trifluoroethanesulfonyl chlorideHCID 566631734-N-[(1R,2R)-2-aminocyclohexyl]-5-chloro-2-N-[3-(2-methoxyethyl)-1,2,4,5-tetrahydro-3-benzazepin-7-yl]pyrimidine-2,4-diamine

Produkt 1

HCID 56666620HCID 56666620, VerbindungAusbeute 53 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

N*4*-((1R,2R)-2-Amino-cyclohexyl)-5-chloro-N*2*-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl]-pyrimidine-2,4-diamine was dissolved in Methylene chloride (5 mL) and Triethylamine (0.15 mL, 1.1 mmol) was added, followed by 2,2,2-Trifluoroethanesulfonyl chloride (0.025 mL, 0.23 mmol). Stir under an atmosphere of Nitrogen at room temperature for 45 min, then partition between 10 mL satd. sodium bicarbonate and 10 mL DCM. Separate and extract the aqueous layer, 3×10 mL DCM. Dry the combined organics over sodium sulfate, filter and concentrate in vacuo. The resultant oil was purified on a sulfonic acid resin cartridge, washing with methanol, eluting with ammonia/methanol. Conc. in vacuo reconcentrating from DCM afforded an oil. Subsequent purification on silica gel (0-10% MeOH:DCM, 12 g SiO2) gave 2,2,2-Trifluoro-ethanesulfonic acid ((1R,2R)-2-{5-chloro-2-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-amide (55 mg, 53%) as a colorless film. LCMS (m/e) 591 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 7.88 (s, 1H), 7.21 (d, 1H, J=7.9 Hz), 7.18 (s, 1H), 7.01 (d, 1H, J=7.9 Hz), 6.97 (s, 1H), 5.36 (d, 1H, J=7.5 Hz), 5.31 (s, 1H), 3.84 (m, 1H), 3.61 (q, 2H, J=9.0 Hz), 3.55 (t, 2H, J=5.4 Hz), 3.36 (s, 3H), 3.29 (m, 1H), 2.9 (m, 4H), 2.72 (m, 6H), 2.17 (m, 2H), 1.82 (m, 2H), 1.34 (m, 4H).

Aufarbeitung

  1. custompartition between 10 mL
  2. customSeparate
  3. extractionextract the aqueous layer, 3×10 mL DCM
  4. dry with materialDry the combined organics over sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customThe resultant oil was purified on a sulfonic acid resin cartridge
  8. washwashing with methanol
  9. washeluting with ammonia/methanol
  10. customafforded an oil
  11. customSubsequent purification on silica gel (0-10% MeOH:DCM, 12 g SiO2)

Quellen und Nachweise

ORD-Eintrag
ord-da440d6d49fc46029b0e9f5e1ae8f82d
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08552186B2

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