Trimethyl orthoformate → (s)-5-(4-(3-Methylmorpholino)-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)thieno[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine

HRID 881571Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 881571
Cl[C:2]1[N:3]=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][C@@H:14]2[CH3:19])[C:5]2[S:10][C:9]([CH:11]=O)=[CH:8][C:6]=2[N:7]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[CH3:34][S:35]([N:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1)(=[O:37])=[O:36].COC(OC)OC.[NH2:51][C:52]1[N:57]=[CH:56][C:55](B2OC(C)(C)C(C)(C)O2)=[CH:54][N:53]=1.CC([O-])=O.[K+]>O.C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC#N.ClCCCl.CC(O)=O>[CH3:19][C@@H:14]1[N:13]([C:4]2[C:5]3[S:10][C:9]([CH2:11][N:41]4[CH2:42][CH2:43][N:38]([S:35]([CH3:34])(=[O:37])=[O:36])[CH2:39][CH2:40]4)=[CH:8][C:6]=3[N:7]=[C:2]([C:55]3[CH:54]=[N:53][C:52]([NH2:51])=[N:57][CH:56]=3)[N:3]=2)[CH2:18][CH2:17][O:16][CH2:15]1

Komponenten

13

Edukt 6

HCID 9005Trimethyl orthoformateHCID 517044Potassium AcetateHCID 7091611-(Methylsulfonyl)piperazineHCID 5049666Sodium triacetoxyborohydrideHCID 177502122-Aminopyrimidine-5-boronic acid, pinacol esterHCID 58234096(S)-2-chloro-4-(3-methylmorpholino)thieno[3,2-d]pyrimidine-6-carbaldehyde

Produkt 1

HCID 24948167(s)-5-(4-(3-Methylmorpholino)-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)thieno[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine

Reagenzien, Katalysatoren, Lösungsmittel 6

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 111,2-DichloroethaneLösungsmittelHCID 176Acetic AcidLösungsmittelHCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Following General Procedure D: (S)-2-chloro-4-(3-methylmorpholino)thieno[3,2-d]pyrimidine-6-carbaldehyde (110 mg, 0.37 mmol), HOAc (22 mg), NaBH(OAc)3 (94 mg, 0.44 mmol), 1-methanesulfonyl piperazine (70 mg, 0.43 mmol), 1,2-dichloroethane (1.0 mL), trimethylorthoformate at room temperature for 1 h. The crude product was used in the next step without purification. MS (Q1) 445 (M)+. Following general procedure A: crude product from above, 2-aminopyrimidine-5-boronic acid pinacol ester (106 mg, 0.48 mmol), Pd(PPh3)4 (30 mg), MeCN (1.5 mL) and 1M KOAc in H2O (1.5 mL) were irradiated at 140° C. for 30 min. The reaction mixture was diluted with CH2Cl2, and filtered. The filtrate was concentrated to give 424, purified by reverse phase HPLC. (28 mg) MS (Q1) 505 (M).

Aufarbeitung

  1. customThe crude product was used in the next step without purification
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated

Quellen und Nachweise

ORD-Eintrag
ord-c50a839ca5db47af9a7cb3e9da9c6b02
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08993563B2

Notizen zur Reaktion

Wird geladen…