Sodium Carbonate → tert-Butyl (1-{4-[2-(1-oxo-1,3-dihydro-2-benzofuran-5-yl)-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl]phenyl}cyclobutyl)carbamate

HRID 1047055Notes

Reaction equation

HRID 1047055 reaction equation
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:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:29][CH2:28][CH2:27]2)=[CH:22][CH:21]=1.CC1(C)C(C)(C)OB([C:46]2[CH:55]=[CH:54][C:49]3[C:50](=[O:53])[O:51][CH2:52][C:48]=3[CH:47]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.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>[O:53]=[C:50]1[C:49]2[CH:54]=[CH:55][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:25]=[CH:24][C:23]([C:26]4([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:35])([CH3:34])[CH3:36])[CH2:29][CH2:28][CH2:27]4)=[CH:22][CH:21]=3)=[CH:47][C:48]=2[CH2:52][O:51]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 580746235-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3H-2-benzofuran-1-oneHCID 136331865tert-butyl {1-[4-(2-bromo-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate

Product 1

HCID 69087728tert-Butyl (1-{4-[2-(1-oxo-1,3-dihydro-2-benzofuran-5-yl)-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl]phenyl}cyclobutyl)carbamateYield 71%

Reagents, catalysts & solvents 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

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, 0.090 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-benzofuran-1(3H)-one (80 mg, ca.0.267 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (6 mg, 0.09 mmol), and 2M Na2CO3 aq. (0.090 mL, 0.18 mmol) in DMF (2.5 mL) was treated with microwave (160° C. for 1 hour). The mixture was diluted with AcOEt, washed with water(×3), brine, dried over Na2SO4, then filtrated through Celite pad. The filtrate was concentrated and the residue was purified by preparative thin-layer chromatography (n-hexane/AcOEt=1:2) to afford the desired product (39 mg, 71%) as a white solid. 1HNMR (CDCl3) 400 MHz δ: 8.15 (dd, J=8.0 Hz and 1.7 Hz, 1H), 8.03 (d, J=4.0 Hz, 1H), 7.87-7.83 (m, 2H), 7.74-7.72 (m, 1H), 7.65-7.59 (m, 2H), 7.41 (d, J=8.6 Hz, 1H), 7.34 (td, J=7.4 Hz and 1.7 Hz, 1H), 7.19-7.16 (m, 2H), 6.97 (d, J=7.4 Hz, 1H), 6.80 (d, J=7.4 Hz, 1H), 6.61 (dd, J=8.0 Hz and 4.6 Hz, 1H), 6.26 (s, 1H), 5.27 (s, 2H), 5.15 (br s, 1H), 2.59-2.52 (m, 2H), 2.50-2.40 (m, 2H), 2.21-2.12 (m, 1H), 1.96-1.87 (m, 1H), 1.39 (br s, 9H). LCMS: 612 [M+H].

Workup

  1. additionwas treated with microwave (160° C. for 1 hour)
  2. washwashed with water(×3), brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltrated through Celite pad
  5. concentrationThe filtrate was concentrated
  6. customthe residue was purified by preparative thin-layer chromatography (n-hexane/AcOEt=1:2)

Sources & evidence

ORD record
ord-a94b0311d79441a7b526fbb2ccc082cf
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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