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 1365470ノート

反応式

HRID 1365470 の反応式
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

参加物

13

反応物 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

生成物 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

試薬・触媒・溶媒 6

HCID 178418397HCID 178418397、化合物触媒HCID 111,2-Dichloroethane溶媒HCID 176Acetic Acid溶媒HCID 962Water溶媒HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

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

出典と根拠

ORDレコード
ord-465f2735758f4513a72b0681c7082333
出典データセット
uspto-grants-2011_02
特許番号
US07888352B2

反応ノート

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