5-(Trifluoromethyl)pyrazin-2-amine → [2-(2,6-Dichloro-benzyl)-thiazolo[5,4-d]pyrimidin-7-yl]-(5-trifluoromethyl-pyrazin-2-yl)-amine

HRID 474310

반응식

HRID 474310 반응식
Cl[C:2]1[C:3]2[N:10]=[C:9]([CH2:11][C:12]3[C:17]([Cl:18])=[CH:16][CH:15]=[CH:14][C:13]=3[Cl:19])[S:8][C:4]=2[N:5]=[CH:6][N:7]=1.[F:20][C:21]([F:30])([F:29])[C:22]1[N:23]=[CH:24][C:25]([NH2:28])=[N:26][CH:27]=1.CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.CC(P(C(C)(C)C)C1[CH-]C=CC=1)(C)C.C1C=CC([C-]2C(C3C=CC=CC=3)=C(C3C=CC=CC=3)C(C3C=CC=CC=3)=C2C2C=CC=CC=2)=CC=1.[Fe+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:19][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]([Cl:18])[C:12]=1[CH2:11][C:9]1[S:8][C:4]2[N:5]=[CH:6][N:7]=[C:2]([NH:28][C:25]3[CH:24]=[N:23][C:22]([C:21]([F:30])([F:20])[F:29])=[CH:27][N:26]=3)[C:3]=2[N:10]=1

참가 물질

7

반응물 3

HCID 133411155-(Trifluoromethyl)pyrazin-2-amineHCID 23676156Sodium t-butoxideHCID 577424637-Chloro-2-(2,6-dichloro-benzyl)-thiazolo[5,4-d]pyrimidine

생성물 1

HCID 42642035[2-(2,6-Dichloro-benzyl)-thiazolo[5,4-d]pyrimidin-7-yl]-(5-trifluoromethyl-pyrazin-2-yl)-amine

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 12024214Ditert-butyl(cyclopenta-1,3-dien-1-yl)phosphane;iron(2+);(2,3,4,5-tetraphenylcyclopenta-1,4-dien-1-yl)benzene촉매HCID 1140Toluene용매

반응 조건

온도
90 °C

실험 절차

To a mixture of 7-chloro-2-(2,6-dichloro-benzyl)-thiazolo[5,4-d]pyrimidine (113 mg, 0.34 mmol), 1,2,3,4,5-pentaphenyl-1-(di-t-butylphosphino)ferrocene (49 mg, 0.07 mmol), tris(dibenzylideneacetone)dipalladium (0) (31 mg, 0.03 mmol), and 5-trifluoromethyl-pyrazin-2-ylamine (66 mg, 0.41 mmol) in toluene (3 mL) was added NaOtBu (40 mg, 0.41 mmol) at rt. The mixture was heated to 90° C. under N2. After 18 h, the reaction mixture was cooled and filtered through a pad of diatomaceous earth, eluting with MeOH (30 mL). The filtrate was concentrated and the crude residue was purified using preparative reverse-phase HPLC to afford the title compound a colorless solid (43 mg, 28%). MS (ESI): mass calcd. for C17H9Cl2F3N6S, 455.9; m/z found, 457.0 [M+H]+. 1H NMR ((CD3)2SO): 10.77 (s, 1H), 9.49 (s, 1H), 8.88-8.87 (m, 1H), 8.75 (s, 1H), 7.59 (d, J=8.0 Hz, 2H), 7.45 (dd, J=8.5, 7.7 Hz, 1H), 4.83 (s, 2H).

후처리

  1. temperaturethe reaction mixture was cooled
  2. filtrationfiltered through a pad of diatomaceous earth
  3. washeluting with MeOH (30 mL)
  4. concentrationThe filtrate was concentrated
  5. customthe crude residue was purified

출처 및 근거

ORD 기록
ord-27cff62b67824d658cde7ceca541d075
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08637527B2

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