Sodium Carbonate → (S)-6-((1-amino-1-oxopropan-2-yl)amino)-2-(4-(benzo[d][1,3]dioxol-5-yloxy)phenyl)pyrimidine-4-carboxamide

HRID 1752447노트

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HRID 1752447 반응식
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([O:10][C:11]3[CH:16]=[CH:15][C:14](B4OC(C)(C)C(C)(C)O4)=[CH:13][CH:12]=3)=[CH:9][C:4]=2[O:3][CH2:2]1.[NH2:26][C:27](=[O:41])[C@@H:28]([NH:30][C:31]1[N:36]=[C:35](Cl)[N:34]=[C:33]([C:38]([NH2:40])=[O:39])[CH:32]=1)[CH3:29].C([O-])([O-])=O.[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCOCC1>[NH2:26][C:27](=[O:41])[CH:28]([NH:30][C:31]1[N:36]=[C:35]([C:14]2[CH:13]=[CH:12][C:11]([O:10][C:8]3[CH:7]=[CH:6][C:5]4[O:1][CH2:2][O:3][C:4]=4[CH:9]=3)=[CH:16][CH:15]=2)[N:34]=[C:33]([C:38]([NH2:40])=[O:39])[CH:32]=1)[CH3:29].[NH2:26][C:27](=[O:41])[C@@H:28]([NH:30][C:31]1[N:36]=[C:35]([C:14]2[CH:13]=[CH:12][C:11]([O:10][C:8]3[CH:7]=[CH:6][C:5]4[O:1][CH2:2][O:3][C:4]=4[CH:9]=3)=[CH:16][CH:15]=2)[N:34]=[C:33]([C:38]([NH2:40])=[O:39])[CH:32]=1)[CH3:29]

참가 물질

7

반응물 3

HCID 10340Sodium CarbonateHCID 712856355-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]-1,3-benzodioxoleHCID 89422280HCID 89422280, 화합물

생성물 2

HCID 71283206(S)-6-((1-amino-1-oxopropan-2-yl)amino)-2-(4-(benzo[d][1,3]dioxol-5-yloxy)phenyl)pyrimidine-4-carboxamide수율 87.2%HCID 71283211HCID 71283211, 화합물

시약·촉매·용매 2

HCID 178418476HCID 178418476, 화합물촉매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

A 50-mL vial with a screw-top septum was charged with 200 mg of 2-(4-(benzo[d][1,3]dioxol-5-yloxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, 1 equivalent of (S)-6-((1-amino-1-oxopropan-2-yl)amino)-2-chloropyrimidine-4-carboxamide (1.53 mg, 0.59 mmol), 1.5 mL 2M aqueous Na2CO3, 0.07 equivalents of PdCl2(PPh3)2 (28 mg, 0.04 mmol), and 8 mL dioxane. The vial was purged with nitrogen and heated to 100° C. for 6 h, at which time the reaction was complete. The mixture was diluted with 100 mL EtOAc and washed two times with 100 mL water. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The residue was chromatographed by combiflash using a 40-gram silica column with a gradient EtOAc (100% max) in hexane to provide 108 mg (43% yield) of S)-6-((1-amino-1-oxopropan-2-yl)amino)-2-(4-(benzo[d][1,3]dioxol-5-yloxy)phenyl)pyrimidine-4-carboxamide as a white solid. m/z 421, 1H NMR (CD3OD): 8.51-8.41 (m, 2H), 7.14-7.07 (s, 1H), 7.01-6.93 (m, 2H), 6.86-6.78 (m, 1H), 6.64-6.60 (m, 1H), 6.57-6.50 (m, 1H), 6.01-5.95 (s, 2H), 4.61-4.49 (m, 1H), 1.56-1.48 (m, 3H).

후처리

  1. customThe vial was purged with nitrogen
  2. additionThe mixture was diluted with 100 mL EtOAc
  3. washwashed two times with 100 mL water
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was chromatographed by combiflash

출처 및 근거

ORD 기록
ord-d35380ee3fdb4cca9664f83241fb106a
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09163008B2

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