Sodium Carbonate → benzyl 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 1047002Notes

Reaction equation

HRID 1047002 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.[CH2:38]([O:45][C:46]([C:48]1[CH:53]=[CH:52][C:51](B(O)O)=[CH:50][CH:49]=1)=[O:47])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.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:51]3[CH:52]=[CH:53][C:48]([C:46]([O:45][CH2:38][C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)=[O:47])=[CH:49][CH:50]=3)=[CH:21][CH:22]=2)[CH2:27][CH2:28][CH2:29]1)=[O:37])([CH3:35])([CH3:34])[CH3:36]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27732514-(Benzyloxycarbonyl)phenylboronic 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 67503647benzyl 4-[3-(4-{1-[(tert-butoxycarbonyl)amino]cyclobutyl}phenyl)-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-2-yl]benzoateYield 51%

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-chloro-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate (150 mg, 0.292 mmol), [4-(benzyloxycarbonyl)phenyl]boronic acid (149 mg, 0.584 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (21 mg, 0.029 mmol), and 2M Na2CO3 aq. (0.292 mL, 0.584 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=1:2) to afford the desired product (102 mg, 51%) as a yellow solid. LCMS: 690 [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-a9e141dabe7d40bd8dac1be1324a7f76
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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