Potassium Phosphate, Tribasic → 1-{4-[2-(1H-pyrrolo[3,2-b]pyridin-6-yl)-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl]phenyl}cyclobutanamine

HRID 1047001ノート

反応式

HRID 1047001 の反応式
Br[C:2]1[N:3]=[C:4]2[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[NH:8][C:7]3[N:15]=[CH:16][CH:17]=[CH:18][C:6]=3[N:5]2[C:19]=1[C:20]1[CH:25]=[CH:24][C:23]([C:26]2([NH:30]C(=O)OC(C)(C)C)[CH2:29][CH2:28][CH2:27]2)=[CH:22][CH:21]=1.CC1(C)C(C)(C)OB([C:46]2[CH:47]=[C:48]3[NH:54][CH:53]=[CH:52][C:49]3=[N:50][CH:51]=2)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.O.CCOC(C)=O.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[NH:54]1[C:48]2[C:49](=[N:50][CH:51]=[C:46]([C:2]3[N:3]=[C:4]4[C:10]5[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=5[NH:8][C:7]5[N:15]=[CH:16][CH:17]=[CH:18][C:6]=5[N:5]4[C:19]=3[C:20]3[CH:21]=[CH:22][C:23]([C:26]4([NH2:30])[CH2:29][CH2:28][CH2:27]4)=[CH:24][CH:25]=3)[CH:47]=2)[CH:52]=[CH:53]1

参加物

7

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 242292706-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo(3,2-b)pyridineHCID 136331865tert-butyl {1-[4-(2-bromo-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate

生成物 1

HCID 569685261-{4-[2-(1H-pyrrolo[3,2-b]pyridin-6-yl)-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl]phenyl}cyclobutanamine収率 71.7%

試薬・触媒・溶媒 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)触媒HCID 8857Ethyl Acetate溶媒HCID 21962138N,N-Dimethylformamide--water (1/1)溶媒

反応条件

温度
160 °C

実験手順

A mixture of tert-butyl {1-[4-(2-bromo-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate (50 mg, 0.09 mmol), 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[3,2-b]pyridine (44 mg, 0.18 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (6.3 mg, 0.01 mmol) and K3PO4 (72 mg, 0.27 mmol) in DMF/water (0.9 mL, 6:1, v/v) was heated at 160° C. under microwave irradiation for 1 hour. After cooling to room temperature, the mixture was diluted with EtOAc and washed with water (×3). The organic layer was dried over anhydrous Na2SO4 and concentrated. The residue was purified by HPLC. The fraction was evaporated to dryness. Step 2: The residue was dissolved in methanol (10 mL) and 4M HCl in dioxane (10 mL) was added. After overnight reaction, the mixture was evaporated and the residue was purified by HPLC to give the titled compound as a white solid (32 mg, 60%). 1HNMR (DMSO-d6) 400 MHz δ: 11.39 (s, 1H), 8.58 (s, 1H), 8.38 (d, J=1.7 Hz, 1H), 8.25 (s, 1H), 8.09 (dd, J=4.6, 1.7 Hz, 1H), 7.99 (dd, J=8.0, 1.7 Hz, 1H), 7.89 (d, J=1.1 Hz, 1H), 7.63 (t, J=3.2 Hz, 1H), 7.49 (d, J=8.6 Hz, 2H), 7.36 (td, J=7.4, 1.7 Hz, 1H), 7.30 (d, J=8.0 Hz, 1H), 7.23 (d, J=8.6 Hz, 2H), 7.13 (t, J=7.4 Hz, 1H), 6.90 (dd, J=7.7, 1.4 Hz, 1H), 6.75 (dd, J=8.0, 4.6 Hz, 1H), 6.51-6.49 (m, 1H), 2.48-2.41 (m, 2H), 2.26-2.19 (m, 2H), 2.11-2.02 (m, 1H), 1.77-1.68 (m, 1H); LCMS: 496 [M+H].

後処理

  1. temperatureAfter cooling to room temperature
  2. washwashed with water (×3)
  3. dry with materialThe organic layer was dried over anhydrous Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by HPLC
  6. customThe fraction was evaporated to dryness
  7. dissolutionStep 2: The residue was dissolved in methanol (10 mL)
  8. addition4M HCl in dioxane (10 mL) was added
  9. customAfter overnight reaction
  10. customthe mixture was evaporated
  11. customthe residue was purified by HPLC

出典と根拠

ORDレコード
ord-344eab8f0cc742b19afabfeed54cea44
出典データセット
uspto-grants-2013_10
特許番号
US08569331B2

反応ノート

読み込み中…