Triethylamine → HCID 67504131, compound

HRID 1047028Notes

Reaction equation

HRID 1047028 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.C(N(CC)CC)C>CN(C=O)C.CO.CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:33]([O:32][C:31]([NH: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:31]([O:32][CH3:33])=[O:37])=[CH:25][CH:24]=2)[CH2:29][CH2:28][CH2:27]1)=[O:37])([CH3:36])([CH3:34])[CH3:35]

Participants

7

Reactant 2

HCID 8471TriethylamineHCID 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 67504131HCID 67504131, compoundYield 74.8%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

tert-butyl {1-[4-(2-bromo-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate (100 mg, 0.179 mmol), triethylamine (0.5 mL), bis(triphenylphosphine)dichloropalladium(II) (38 mg, 0.054 mmol) were dissolved in DMF (3 mL) and MeOH (3 mL). Atmosphere of the mixture was exchanged to CO gas, then heated to 100° C. for 88 hours. 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=1:2×3) to afford the desired product (36 mg, 37%) as a colorless oil. 1HNMR (CDCl3) 400 MHz δ: 8.13 (dd, J=8.0 Hz and 1.7 Hz, 1H), 8.02 (d, J=4.0 Hz, 1H), 7.40 (d, J=8.0 Hz, 2H), 7.33 (td, J=7.4 Hz and 1.7 Hz, 2H), 7.30-7.24 (m, 4H), 7.14 (td, J=7.4 Hz and 1.1 Hz, 1H), 6.95 (d, J=7.4 Hz, 1H), 6.82-6.78 (m, 1H), 6.59 (dd, J=8.0 Hz and 4.6 Hz, 1H), 6.24 (s, 1H), 5.11 (br s, 1H), 3.88 (s, 3H), 2.57-2.42 (m, 4H), 2.17-2.08 (m, 1H), 1.91-1.83 (m, 1H), 1.39 (br s, 9H). LCMS: 538 [M+H].

Workup

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

Sources & evidence

ORD record
ord-490879c40cdd4bcaa3fbdd4965d673d1
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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