Trimethyl orthoformate → (s)-1-(4-((2-(2-Aminopyrimidin-5-yl)-4-(3-methylmorpholino)thieno[3,2-d]pyrimidin-6-yl)methyl)-1,4-diazepan-1-yl)ethanone

HRID 881572ノート

反応式

HRID 881572 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+].[C:34]([N:37]1[CH2:43][CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1)(=[O:36])[CH3:35].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>[NH2:51][C:52]1[N:57]=[CH:56][C:55]([C:2]2[N:3]=[C:4]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][C@@H:14]3[CH3:19])[C:5]3[S:10][C:9]([CH2:11][N:40]4[CH2:41][CH2:42][CH2:43][N:37]([C:34](=[O:36])[CH3:35])[CH2:38][CH2:39]4)=[CH:8][C:6]=3[N:7]=2)=[CH:54][N:53]=1

参加物

13

反応物 6

HCID 9005Trimethyl orthoformateHCID 517044Potassium AcetateHCID 4186202N-AcetylhomopiperazineHCID 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 24948166(s)-1-(4-((2-(2-Aminopyrimidin-5-yl)-4-(3-methylmorpholino)thieno[3,2-d]pyrimidin-6-yl)methyl)-1,4-diazepan-1-yl)ethanone

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 (101 mg, 0.48 mmol), N-acetylhomopiperazine (63 mg, 0.44 mmol), 1,2-dichloroethane (1.0 mL), trimethylorthoformate were reacted at room temperature for 2 h. The crude product was used in the next step without purification. MS (Q1) 424 (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 crude 425 which was purified by reverse phase HPLC (68 mg). MS (Q1) 483 (M)+

後処理

  1. customwere reacted at room temperature for 2 h
  2. customThe crude product was used in the next step without purification
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated
  5. customto give crude 425 which
  6. customwas purified by reverse phase HPLC (68 mg)

出典と根拠

ORDレコード
ord-40d1329740df4134a6ee8dcc6c71421c
出典データセット
uspto-grants-2015_03
特許番号
US08993563B2

反応ノート

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