Sodium Carbonate → HCID 68067214, compound

HRID 1047007Notes

Reaction equation

HRID 1047007 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.[C:38]([C:41]1[CH:42]=[C:43](B(O)O)[CH:44]=[CH:45][CH:46]=1)(=[O:40])[CH3:39].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:38]([C:41]1[CH:42]=[CH:43][C:44]([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:21]=[CH:22][C:23]([C:26]3([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:34])[CH3:35])[CH2:29][CH2:28][CH2:27]3)=[CH:24][CH:25]=2)=[CH:45][CH:46]=1)(=[O:40])[CH3:39]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27343103-Acetylphenylboronic 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 68067214HCID 68067214, compoundYield 77.9%

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 (30 mg, 0.058 mmol), m-acetylphenyl boronic acid (19 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 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=1:1×2) to afford the desired product (27 mg, 77%) as a yellow solid. 1HNMR (CDCl3) 400 MHz δ: 8.17 (dd, J=7.7, 1.4 Hz, 1H), 8.02 (d, J=4.6 Hz, 1H), 7.86 (d, J=8.6 Hz, 2H), 7.68 (d, J=8.6 Hz, 2H), 7.40 (d, J=8.0 Hz, 2H), 7.32 (td, J=8.0, 1.7 Hz, 1H), 7.18-7.15 (m, 2H), 6.96 (d, J=8.0 Hz, 1H), 6.80 (d, J=7.4 Hz, 1H), 6.60 (dd, J=8.0, 5.2 Hz, 1H), 6.25 (s, 1H), 5.13 (br s, 2H), 2.59-2.53 (m, 5H), 2.50-2.42 (m, 2H), 2.21-2.12 (m, 1H), 1.95-1.87 (m, 1H), 1.40 (br s, 9H). LCMS: 598 [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=1:1×2)

Sources & evidence

ORD record
ord-4a1316fd380f429698cf9938ce715647
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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