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

HRID 60204

反応式

HRID 60204 の反応式
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.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.[F:45][C:46]([F:55])([F:54])[C:47]1[CH:48]=[CH:49][C:50]([NH2:53])=[N:51][CH:52]=1.CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[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:53][C:50]3[CH:49]=[CH:48][C:47]([C:46]([F:54])([F:45])[F:55])=[CH:52][N:51]=3)[C:3]=2[N:10]=1

参加物

7

反応物 4

HCID 7358622-Amino-5-(trifluoromethyl)pyridineHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 577424637-Chloro-2-(2,6-dichloro-benzyl)-thiazolo[5,4-d]pyrimidine

生成物 1

HCID 42642034[2-(2,6-Dichloro-benzyl)-thiazolo[5,4-d]pyrimidin-7-yl]-(5-trifluoromethyl-pyridin-2-yl)-amine

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 1140Toluene溶媒

反応条件

温度
90 °C

実験手順

To a mixture of 7-chloro-2-(2,6-dichloro-benzyl)-thiazolo[5,4-d]pyrimidine (120 mg, 0.36 mmol), 2-(dicyclohexylphosphino)biphenyl (25 mg, 0.07 mmol), palladium acetate (8.0 mg, 0.04 mmol), and 5-trifluoromethyl-pyridin-2-ylamine (88 mg, 0.54 mmol) in toluene (3 mL) was added NaOtBu (49 mg, 0.51 mmol) at rt. The mixture was heated to 90° C. for 18 h under N2. The reaction mixture was cooled and filtered through a pad of diatomaceous earth, eluting with EtOAc (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 (95 mg, 58%). MS (ESI): mass calcd. for C18H10Cl2F3N5S, 455.0; m/z found, 456.0 [M+H]+. 1H NMR ((CD3)250): 9.76 (s, 1H), 8.73-8.71 (m, 2H), 8.50 (d, J=8.8 Hz, 1H), 8.23 (dd, J=8.9, 2.4 Hz, 1H), 7.60 (d, J=8.1 Hz, 2H), 7.45 (dd, J=8.5, 7.7 Hz, 1H), 4.83 (s, 2H).

後処理

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

出典と根拠

ORDレコード
ord-87f11bf664a6408e9020377eda3c388f
出典データセット
uspto-grants-2016_09
特許番号
US09440978B2

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