Potassium Phosphate, Tribasic → 5-{3-[4-(1-aminocyclobutyl)phenyl]-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-2-yl}-2-methylphenol

HRID 1047018Notes

Reaction equation

HRID 1047018 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(=O)OC(C)(C)C)[CH2:29][CH2:28][CH2:27]2)=[CH:22][CH:21]=1.[OH:38][C:39]1[CH:40]=[C:41](B(O)O)[CH:42]=[CH:43][C:44]=1[CH3:45].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.O.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>[NH2:30][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:41]3[CH:42]=[CH:43][C:44]([CH3:45])=[C:39]([OH:38])[CH:40]=3)=[CH:21][CH:22]=2)[CH2:27][CH2:28][CH2:29]1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 4187664(3-Hydroxy-4-methylphenyl)boronic acidHCID 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 675037525-{3-[4-(1-aminocyclobutyl)phenyl]-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-2-yl}-2-methylphenolYield 2.3%

Reagents, catalysts & solvents 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 8857Ethyl AcetateSolventHCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Conditions

Temperature
160 °C

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, 0.09 mmol), (3-hydroxy-4-methylphenyl)boronic acid (27 mg, 0.18 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (6.3 mg, 0.01 mmol) and K3PO4 (72 mg, 0.27 mmol) in DMF/water (0.9 mL, 6:1, v/v) was heated at 160° C. under microwave irradiation for 1 hour. After cooling to room temperature, the mixture was diluted with EtOAc and washed with water (×3). The organic layer was dried over anhydrous Na2SO4 and concentrated. The residue was purified by HPLC. The fraction was evaporated and the residue was dissolved in methanol (10 mL) and 4M HCl in dioxane (10 mL). After overnight reaction, the mixture was evaporated and the residue was purified by HPLC to give the titled compound as a white solid (1 mg, 2%). LCMS: 486 [M+H].

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed with water (×3)
  3. dry with materialThe organic layer was dried over anhydrous Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by HPLC
  6. customThe fraction was evaporated
  7. dissolutionthe residue was dissolved in methanol (10 mL)
  8. customAfter overnight reaction
  9. customthe mixture was evaporated
  10. customthe residue was purified by HPLC

Sources & evidence

ORD record
ord-d0528109c6754ebbb36ae712b19a8bc1
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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