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Potassium Phosphate, Tribasic → 5-{3-[4-(1-aminocyclobutyl)phenyl]-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-2-yl}pyrimidin-2-amine

HRID 1047017
ノート
印刷プレビュー

反応式

HRID 1047017 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.C(OC([N:45]([C:53]1[N:58]=[CH:57][C:56](B2OC(C)(C)C(C)(C)O2)=[CH:55][N:54]=1)C(OC(C)(C)C)=O)=O)(C)(C)C.[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>[NH2:30][C:26]1([C:23]2[CH:22]=[CH:21][C:20]([C:19]3[N:5]4[C:6]5[CH:18]=[CH:17][CH:16]=[N:15][C:7]=5[NH:8][C:9]5[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=5[C:4]4=[N:3][C:2]=3[C:56]3[CH:57]=[N:58][C:53]([NH2:45])=[N:54][CH:55]=3)=[CH:25][CH:24]=2)[CH2:29][CH2:28][CH2:27]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 11977092tert-butyl N-[(tert-butoxy)carbonyl]-N-[5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl]carbamateHCID 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 675046355-{3-[4-(1-aminocyclobutyl)phenyl]-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-2-yl}pyrimidin-2-amine収率 56.4%

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), di-tert-butyl[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl]imidodicarbonate (75 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 and the residue was dissolved in methanol (10 mL) and 4M HCl in dioxane (10 mL). After overnight reaction, the mixture was evaporated and the residue was purified by HPLC to give the titled compound as a white solid (24 mg, 43%). 1HNMR (DMSO-d6) 400 MHz δ: 8.56 (s, 1H), 8.26 (d, J=15.5 Hz, 2H), 8.08 (dd, J=4.6, 1.7 Hz, 1H), 7.93 (dd, J=8.0, 1.7 Hz, 1H), 7.50 (d, J=8.6 Hz, 2H), 7.35 (td, J=7.6, 1.5 Hz, 1H), 7.28 (d, J=7.4 Hz, 1H), 7.21 (d, J=8.6 Hz, 2H), 7.10 (t, J=7.4 Hz, 1H), 6.89 (dd, J=8.0, 1.7 Hz, 1H), 6.75 (dd, J=8.0, 4.6 Hz, 1H), 6.72 (s, 2H), 2.45-2.38 (m, 2H), 2.23-2.16 (m, 2H), 2.10-2.00 (m, 1H), 1.75-1.66 (m, 1H); LCMS: 473 [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
  7. dissolutionthe residue was dissolved in methanol (10 mL)
  8. customAfter overnight reaction
  9. customthe mixture was evaporated
  10. customthe residue was purified by HPLC

出典と根拠

ORDレコード
ord-53628a55b2b04ed4b49f5b9b97273a3c
出典データセット
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08569331B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート