Potassium Phosphate, Tribasic → HCID 67503458, compound

HRID 1047023Notes

Reaction equation

HRID 1047023 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.CC1(C)C(C)(C)OB([C:46]2[CH:47]=[CH:48][C:49]([N:52]3[CH2:57][CH2:56][O:55][CH2:54][CH2:53]3)=[N:50][CH:51]=2)O1.[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>[N:52]1([C:49]2[N:50]=[CH:51][C:46]([C:2]3[N:3]=[C:4]4[C:10]5[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=5[NH:8][C:7]5[N:15]=[CH:16][CH:17]=[CH:18][C:6]=5[N:5]4[C:19]=3[C:20]3[CH:21]=[CH:22][C:23]([C:26]4([NH2:30])[CH2:29][CH2:28][CH2:27]4)=[CH:24][CH:25]=3)=[CH:47][CH:48]=2)[CH2:53][CH2:54][O:55][CH2:56][CH2:57]1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27953634-(5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridinyl)morpholineHCID 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 67503458HCID 67503458, compoundYield 49.2%

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), 4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]morpholine (52 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. To the fraction, conc. HCl (3 ml) and methanol (3 ml) were added and the residue was evaporated after 24 h. The residue was purified by HPLC to give the titled compound as a white solid (24 mg, 39%). 1HNMR (DMSO-d6) 400 MHz δ: 8.54 (s, 1H), 8.26 (s, 1H), 8.21 (d, J=2.3 Hz, 1H), 8.07 (dd, J=4.9, 1.4 Hz, 1H), 7.93 (dd, J=7.7, 1.4 Hz, 1H), 7.70 (dd, J=8.9, 2.6 Hz, 1H), 7.49 (d, J=8.6 Hz, 2H), 7.34 (t, J=7.4 Hz, 1H), 7.28 (d, J=7.4 Hz, 1H), 7.21 (d, J=8.6 Hz, 2H), 7.11 (t, J=7.4 Hz, 1H), 6.86 (dd, J=8.0, 1.1 Hz, 1H), 6.81 (d, J=9.2 Hz, 1H), 6.73 (dd, J=7.7, 4.9 Hz, 1H), 3.68 (t, J=4.9 Hz, 4H), 3.43 (t, J=5.2 Hz, 4H), 2.45-2.38 (m, 2H), 2.22-2.15 (m, 2H), 2.10-2.01 (m, 1H), 1.75-1.67 (m, 1H); LCMS: 542 [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. additionTo the fraction, conc. HCl (3 ml) and methanol (3 ml) were added
  7. customthe residue was evaporated after 24 h
  8. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-4d892f214f2841bb8845f575b667da83
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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