Sodium Carbonate → HCID 69087677, compound

HRID 1047067Notes

Reaction equation

HRID 1047067 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][O:39][C:40]1[CH:45]=[CH:44][C:43]([C:46]2[CH:51]=[CH:50][C:49](B3OC(C)(C)C(C)(C)O3)=[CH:48][N:47]=2)=[CH:42][CH:41]=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](=[O:37])[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:49]3[CH:48]=[N:47][C:46]([C:43]4[CH:42]=[CH:41][C:40]([O:39][CH3:38])=[CH:45][CH:44]=4)=[CH:51][CH:50]=3)=[CH:21][CH:22]=2)[CH2:27][CH2:28][CH2:29]1)([CH3:36])([CH3:35])[CH3:34]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 67503159HCID 67503159, compoundHCID 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 69087677HCID 69087677, compoundYield 102.3%

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), 2-(4-methoxyphenyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (84 mg, 0.27 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (6 mg, 0.09 mmol), and 2M Na2CO3 aq. (0.090 mL, 0.18 mmol) in DMF (2.5 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) to afford the desired product (61 mg, quant) as a yellow solid. 1HNMR (CDCl3) 400 MHz δ: 8.79 (d, J=2.3 Hz, 1H), 8.17 (dd, J=7.4 Hz and 1.7 Hz, 1H), 8.06-8.00 (m, 2H), 7.95 (d, J=8.6 Hz, 2H), 7.63 (d, J=8.6 Hz, 1H), 7.39 (d, J=8.0 Hz, 2H), 7.32 (td, J=7.4 Hz and 1.7 Hz, 1H), 7.20 (d, J=8.0 Hz, 1H), 7.17 (td, J=8.0 Hz and 1.7 Hz, 1H), 7.00-6.95 (m, 3H), 6.83-6.78 (m, 1H), 6.61 (dd, J=8.0 Hz and 4.6 Hz, 1H), 6.26 (s, 1H), 5.12 (br s, 1H), 3.86 (s, 3H), 2.58-2.42 (m, 4H), 2.18-2.11 (m, 1H), 1.94-1.87 (m, 1H), 1.40 (br s, 9H). LCMS: 663 [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)

Sources & evidence

ORD record
ord-ebd56147c2424f7aa8b4f86d69e77df2
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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