Sodium Carbonate → Methyl 4-[3-(4-{1-[(tert-butoxycarbonyl)amino]cyclobutyl}phenyl)-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-2-yl]benzoate

HRID 1046999Notes

Reaction equation

HRID 1046999 reaction equation
Cl[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][O:39][C:40]([C:42]1[CH:47]=[CH:46][C:45](B(O)O)=[CH:44][CH:43]=1)=[O: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:33]([O:32][C:31]([NH: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:45]3[CH:46]=[CH:47][C:42]([C:40]([O:39][CH3:38])=[O:41])=[CH:43][CH:44]=3)=[CH:21][CH:22]=2)[CH2:27][CH2:28][CH2:29]1)=[O:37])([CH3:34])([CH3:36])[CH3:35]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27343694-Methoxycarbonylphenylboronic acidHCID 136331866tert-butyl {1-[4-(2-chloro-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate

Product 1

HCID 67504209Methyl 4-[3-(4-{1-[(tert-butoxycarbonyl)amino]cyclobutyl}phenyl)-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-2-yl]benzoateYield 78.7%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
160 °C

Procedure

A mixture of tert-butyl {1-[4-(2-chloro-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate (30 mg, 0.058 mmol), [4-(methoxy carbonyl)phenyl]boronic acid (21 mg, 0.12 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (4 mg, 0.006 mmol), and 2M Na2CO3 aq. (0.058 mL, 0.12 mmol) in DMF (1 mL) was heated in microwave oven at 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=1:1) to afford the desired product (28 mg, 78%) as a white solid. 1HNMR (CDCl3) 400 MHz δ: 8.17 (dd, J=8.0 Hz and 1.7 Hz, 1H), 8.02 (d, J=4.0 Hz, 1H), 7.93 (d, J=8.6 Hz, 2H), 7.65 (d, J=8.0 Hz, 2H), 7.38 (d, J=8.0 Hz, 2H), 7.32 (td, J=7.4, 1.1 Hz, 1H), 7.18-7.15 (m, 2H), 6.95 (d, J=8.0 Hz, 1H), 6.80 (d, J=7.4 Hz, 1H), 6.60 (dd, J=8.0 Hz and 4.6 Hz, 1H), 6.25 (s, 1H), 5.13 (br s, 1H), 3.90 (s, 3H), 2.58-2.41 (m, 4H), 2.20-2.11 (m, 1H), 1.95-1.87 (m, 1H), 1.40 (br s, 9H). LCMS: 614 [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=1:1)

Sources & evidence

ORD record
ord-5afc9b3a209747a49ff439cbc80a5943
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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