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

HRID 1047071Notes

Reaction equation

HRID 1047071 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.[CH3:38][N:39]([C:43]1[CH:48]=[CH:47][C:46](B2OC(C)(C)C(C)(C)O2)=[CH:45][CH:44]=1)[C:40](=[O:42])[CH3:41].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>[C:40]([N:39]([CH3:38])[C:43]1[CH:48]=[CH:47][C:46]([C:2]2[N:3]=[C:4]3[C:10]4[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=4[NH:8][C:7]4[N:15]=[CH:16][CH:17]=[CH:18][C:6]=4[N:5]3[C:19]=2[C:20]2[CH:25]=[CH:24][C:23]([C:26]3([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:34])([CH3:35])[CH3:36])[CH2:27][CH2:28][CH2:29]3)=[CH:22][CH:21]=2)=[CH:45][CH:44]=1)(=[O:42])[CH3:41]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 59232387N-methyl-N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamideHCID 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 69087686tert-Butyl {1-[4-(2-{4-[acetyl(methyl)amino]phenyl}-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamateYield 53.2%

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), N-methyl-N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]acetamide (49 mg, 0.18 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (6 mg, 0.009 mmol), and 2M Na2CO3 aq. (0.090 mL, 0.18 mmol) in DMF (3 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=1:4) to afford the desired product (30 mg, 53%) as a pale pink solid. 1HNMR (CDCl3) 400 MHz δ: 8.16 (dd, J=8.0 Hz and 1.7 Hz, 1H), 8.02 (d, J=2.9 Hz, 1H), 7.63 (d, J=8.0 Hz, 2H), 7.39 (d, J=8.0 Hz, 2H), 7.32 (td, J=8.0 Hz and 1.7 Hz, 2H), 7.18 (d, J=8.0 Hz, 2H), 7.16 (t, J=8.0 Hz, 1H), 7.06 (d, J=8.0 Hz, 2H), 6.96 (d, J=8.0 Hz, 1H), 6.81 (d, J=8.0 Hz, 1H), 6.61 (dd, J=8.0 Hz and 4.6 Hz, 1H), 6.27 (s, 1H), 5.13 (br s, 1H), 3.26 (s, 3H), 2.58-2.52 (m, 2H), 2.51-2.39 (m, 2H), 2.19-2.13 (m, 1H), 1.95-1.85 (m, 4H), 1.39 (br s, 9H). LCMS: 627 [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=1:4)

Sources & evidence

ORD record
ord-5d9a3e28885f403ebd410b9b96d0179a
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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