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

HRID 1047019
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HRID 1047019 반응식
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.[CH2:38]([O:40][C:41](=[O:53])[CH2:42][CH2:43][C:44]1[CH:49]=[CH:48][C:47](B(O)O)=[CH:46][CH:45]=1)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:24]=[CH:25][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:47]3[CH:48]=[CH:49][C:44]([CH2:43][CH2:42][C:41]([O:40][CH3:38])=[O:53])=[CH:45][CH:46]=3)=[CH:21][CH:22]=2)[CH2:27][CH2:28][CH2:29]1
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참가 물질

7

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 38517004-(2-Ethoxycarbonylethyl)benzeneboronic acidHCID 136331865tert-butyl {1-[4-(2-bromo-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate

생성물 1

HCID 56956263methyl 3-(4-{3-[4-(1-aminocyclobutyl)phenyl]-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-2-yl}phenyl)propanoate수율 49.2%

시약·촉매·용매 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)촉매
HCID 8857Ethyl Acetate용매
HCID 21962138N,N-Dimethylformamide--water (1/1)용매

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온도
160 °C

실험 절차

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), [4-(3-ethoxy-3-oxopropyl)phenyl]boronic acid (40 mg, 0.18 mmol), bis(di-tert-butyl(4-dimethylamino phenyl)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. To the fraction, conc. HCl (3 ml) and methanol (3 ml) were added and the residue was evaporated after 24 h. The residue was purified by HPLC to give the titled compound as a white solid (24 mg, 42%). 1HNMR (DMSO-d6) 400 MHz δ: 8.54 (s, 1H), 8.22 (s, 1H), 8.07 (dd, J=4.6, 1.7 Hz, 1H), 7.94 (dd, J=7.7, 1.4 Hz, 1H), 7.47 (d, J=8.6 Hz, 2H), 7.42 (d, J=8.6 Hz, 2H), 7.34 (td, J=7.7, 1.5 Hz, 1H), 7.28 (dd, J=8.0, 1.1 Hz, 1H), 7.19 (d, J=8.0 Hz, 2H), 7.14 (d, J=8.6 Hz, 2H), 7.11 (t, J=8.0 Hz, 1H), 6.86 (dd, J=8.0, 1.1 Hz, 1H), 6.72 (dd, J=7.7, 4.9 Hz, 1H), 3.58 (s, 3H), 2.83 (t, J=7.4 Hz, 2H), 2.63 (t, J=8.0 Hz, 2H), 2.43-2.36 (m, 2H), 2.20-2.13 (m, 2H), 2.09-2.00 (m, 1H), 1.75-1.66 (m, 1H); LCMS: 542 [M+H].

후처리

  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. additionTo the fraction, conc. HCl (3 ml) and methanol (3 ml) were added
  7. customthe residue was evaporated after 24 h
  8. customThe residue was purified by HPLC

출처 및 근거

ORD 기록
ord-11e06b255cc3422cb29ecd28cf44f138
출처 데이터셋
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08569331B2

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