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O-Phenylenediamine → N-[4-morpholin-4-yl-6-(3-morpholin-4-yl-azetidin-1-ylmethyl)-thieno[3,2-d]pyrimidin-2-yl]benzene-1,2-diamine

HRID 1922936
ノート
印刷プレビュー

反応式

HRID 1922936 の反応式
Cl[C:2]1[N:3]=[C:4]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[C:5]2[S:10][C:9]([CH2:11][N:12]3[CH2:15][CH:14]([N:16]4[CH2:21][CH2:20][O:19][CH2:18][CH2:17]4)[CH2:13]3)=[CH:8][C:6]=2[N:7]=1.[NH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[NH2:35].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.CC(O)=O.CC(O)=O.[Pd]>[N:22]1([C:4]2[C:5]3[S:10][C:9]([CH2:11][N:12]4[CH2:15][CH:14]([N:16]5[CH2:21][CH2:20][O:19][CH2:18][CH2:17]5)[CH2:13]4)=[CH:8][C:6]=3[N:7]=[C:2]([NH:28][C:29]3[C:30]([NH2:35])=[CH:31][CH:32]=[CH:33][CH:34]=3)[N:3]=2)[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 7243O-PhenylenediamineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 596053422-Chloro-4-morpholin-4-yl-6-(3-morpholin-4-ylazetidin-1-ylmethyl)thieno[3,2-d]pyrimidine

生成物 1

HCID 59606113N-[4-morpholin-4-yl-6-(3-morpholin-4-yl-azetidin-1-ylmethyl)-thieno[3,2-d]pyrimidin-2-yl]benzene-1,2-diamine収率 66%

試薬・触媒・溶媒 2

HCID 4144353Palladium (II) acetate触媒HCID 312751,4-Dioxane溶媒

実験手順

A degassed mixture of 2-chloro-4-morpholin-4-yl-6-(3-morpholin-4-yl-azetidin-1-ylmethyl)thieno[3,2-d]pyrimidine (400 mg, 0.98 mmol), 1,2-diaminobenzene (240 mg, 2.22 mmol), Pd(Oac)2 (64 mg, 0.29 mmol), rac-BINAP (88 mg, 0.14 mmol) and Cs2CO3 (480 mg, 1.47 mmol) in 1,4-dioxane (4 mL)) was subjected to microwave irradiation at 150° C. for 30 minutes. The reaction mixture was cooled to ambient temperature and loaded onto an Isolute® SCX-2 cartridge (25 g). The cartridge was then washed with MeOH and the desired product was subsequently eluted using 2 M NH3 in MeOH. The product was collected and concentrated in vacuo. The resultant residue was purified by flash chromatography (Si—PPC, DCM: 2 M NH3 in MeOH 100:0 to 98:2 to 96:4) to afford N-[4-morpholin-4-yl-6-(3-morpholin-4-yl-azetidin-1-ylmethyl)thieno[3,2-d]pyrimidin-2-yl]benzene-1,2-diamine as a pale yellow oil (310 mg, 66%). LCMS (Method C): RT=2.06 min, [M+H]− 482.4

後処理

  1. customirradiation at 150° C. for 30 minutes
  2. washThe cartridge was then washed with MeOH
  3. washthe desired product was subsequently eluted
  4. customThe product was collected
  5. concentrationconcentrated in vacuo
  6. customThe resultant residue was purified by flash chromatography (Si—PPC, DCM: 2 M NH3 in MeOH 100:0 to 98:2 to 96:4)

出典と根拠

ORDレコード
ord-48443c43f9d64f58ab01e9c59d18be93
出典データセット
uspto-grants-2012_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08173650B2

反応ノート

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