Toluene → 2-(3-Chloro-4-fluorophenyl)-N5-(3,3-dimethylcyclobutyl)-6,7-dihydropyrazolo[1,5-a]pyrazine-3,5(4H)-dicarboxamide

HRID 920771ノート

反応式

HRID 920771 の反応式
CC1(C)CC([C:6]([OH:8])=O)C1.C1C=CC(P([N:24]=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.[Cl:27][C:28]1[CH:29]=[C:30]([C:35]2[C:43]([C:44]([NH2:46])=[O:45])=[C:38]3[CH2:39][NH:40][CH2:41][CH2:42][N:37]3[N:36]=2)[CH:31]=[CH:32][C:33]=1[F:34].[C:47]1([CH3:53])[CH:52]=[CH:51][CH:50]=C[CH:48]=1>CN(C=O)C>[Cl:27][C:28]1[CH:29]=[C:30]([C:35]2[C:43]([C:44]([NH2:46])=[O:45])=[C:38]3[CH2:39][N:40]([C:6]([NH:24][CH:51]4[CH2:52][C:47]([CH3:48])([CH3:53])[CH2:50]4)=[O:8])[CH2:41][CH2:42][N:37]3[N:36]=2)[CH:31]=[CH:32][C:33]=1[F:34]

参加物

6

反応物 4

HCID 1140TolueneHCID 199401P,P-Diphenylphosphinic azideHCID 2151063,3-Dimethylcyclobutanecarboxylic acidHCID 1180616272-(3-Chloro-4-fluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-carboxamide

生成物 1

HCID 1180628512-(3-Chloro-4-fluorophenyl)-N5-(3,3-dimethylcyclobutyl)-6,7-dihydropyrazolo[1,5-a]pyrazine-3,5(4H)-dicarboxamide収率 46%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
90 °C

実験手順

To a stirred solution of Intermediate 285D (13 mg, 0.1 mmol) in toluene (2 ml) was added TEA (0.071 ml, 0.509 mmol), DPPA (0.028 ml, 0.122 mmol) and the reaction mixture was heated to 90° C. for 1 h. The reaction mixture was cooled to RT and to it was added a solution of Intermediate 185B (30 mg, 0.102 mmol) in DMF (1 mL) and stirred at RT for 16 h. The reaction mixture was quenched with 10% NaHCO3 and extracted with ethyl acetate (2×20 mL). The combined organic layer was dried over Na2SO4, filtered and the filtrate evaporated under reduced pressure. The crude product was purified by preparative HPLC to afford Compound 285 (20 mg, 46%). HPLC retention times 9.40 min. and 8.50 min (Methods A and B respectively). MS(ES): m/z=420 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.81-7.90 (m, 1H), 7.64-7.74 (m, 1H), 7.42-7.46 (m, 1H), 7.14-7.40 (d, 2H), 6.98 (s, 1H), 4.72 (s, 2H), 4.06-4.20 (m, 3H), 3.82 (t, J=5.27 Hz, 2H), 1.95-2.05 (m, 2H), 1.72-1.83 (m, 2H), 1.11 (d, J=7.53 Hz, 6H).

後処理

  1. temperatureThe reaction mixture was cooled to RT and to it
  2. customThe reaction mixture was quenched with 10% NaHCO3
  3. extractionextracted with ethyl acetate (2×20 mL)
  4. dry with materialThe combined organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. customthe filtrate evaporated under reduced pressure
  7. customThe crude product was purified by preparative HPLC

出典と根拠

ORDレコード
ord-20b3f2a2b39b406793ae5de6d2dfd515
出典データセット
uspto-grants-2016_03
特許番号
US09273058B2

反応ノート

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