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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
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HRID 1922936 반응식
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
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참가 물질

7

반응물 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

생성물 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-diamine수율 66%

시약·촉매·용매 2

HCID 4144353Palladium (II) acetate촉매HCID 312751,4-Dioxane용매

실험 절차

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

후처리

  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)

출처 및 근거

ORD 기록
ord-48443c43f9d64f58ab01e9c59d18be93
출처 데이터셋
uspto-grants-2012_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08173650B2

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