Sodium Carbonate → 7-Cyclobutyl-5-(2-phenylquinazolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

HRID 422648Notes

Reaction equation

HRID 422648 reaction equation
[C:1]1([C:7]2[N:16]=[CH:15][C:14]3[C:9](=[CH:10][C:11](B4OC(C)(C)C(C)(C)O4)=[CH:12][CH:13]=3)[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:26]1([N:30]2[C:34]3[N:35]=[CH:36][N:37]=[C:38]([NH2:39])[C:33]=3[C:32](I)=[CH:31]2)[CH2:29][CH2:28][CH2:27]1.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:26]1([N:30]2[C:34]3[N:35]=[CH:36][N:37]=[C:38]([NH2:39])[C:33]=3[C:32]([C:11]3[CH:10]=[C:9]4[C:14]([CH:15]=[N:16][C:7]([C:1]5[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=5)=[N:8]4)=[CH:13][CH:12]=3)=[CH:31]2)[CH2:27][CH2:28][CH2:29]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 536290492-Phenyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinazolineHCID 576810747-cyclobutyl-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Product 1

HCID 536290487-Cyclobutyl-5-(2-phenylquinazolin-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

A flask equipped with a reflux condenser was charged with 2-phenyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinazoline (67 mg, 0.20 mmol), 7-cyclobutyl-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-amine (64 mg, 0.20 mmol) and Na2CO3 (56 mg, 0.51 mmol). The reaction setup was evacuated and refilled with Ar (3×). Pd(PPh3)4 (24 mg, 0.021 mmol) was added swiftly minimizing exposure to air and the system was evacuated and refilled with Ar (3×) again. Degassed solvent mixture H2O-DMF (1:5 v/v, 5 mL) was added and the reaction mixture was heated at 80° C. for 42 h. The resulting orange-light brown solution was partitioned between DCM (˜80 mL) and H2O (10 mL). The aqueous layer was extracted with DCM (3×). Combined organics were washed with brine, dried (Na2SO4) and concentrated under reduced pressure (125 mg). Purification by flash chromatography (silica gel, 25 g, 0-2% MeOH in DCM) provided the title compound as a pale yellow solid; The material was also later triturated (hexane 2×, Et2O 1×); 1H NMR (400 MHz, CDCl3) δ 9.46 (d, J=0.8 Hz, 1H), 8.65-8.58 (m, 2H), 8.35 (s, 1H), 8.16 (s, 1H), 8.00 (d, J=8.4 Hz, 1H), 7.75 (dd, J=2.0 Hz, 8.4 Hz, 1H), 7.56-7.46 (m, 3H), 7.39 (s, 1H), 5.44 (br, 2H), 5.33 (quintet, J=8.2 Hz, 1H), 2.67-2.40 (m, 4H), 2.17-1.89 (m, 2H). MS (ES+): m/z 393.1 (100) [MH+]; HPLC: tR=2.91 min (OpenLynx, polar—5 min).

Workup

  1. customA flask equipped with a reflux condenser
  2. customThe reaction setup was evacuated
  3. additionrefilled with Ar (3×)
  4. customthe system was evacuated
  5. additionrefilled with Ar (3×) again
  6. additionDegassed solvent mixture H2O-DMF (1:5 v/v, 5 mL) was added
  7. customThe resulting orange-light brown solution was partitioned between DCM (˜80 mL) and H2O (10 mL)
  8. extractionThe aqueous layer was extracted with DCM (3×)
  9. washCombined organics were washed with brine
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated under reduced pressure (125 mg)
  12. customPurification by flash chromatography (silica gel, 25 g, 0-2% MeOH in DCM)

Sources & evidence

ORD record
ord-123f95b0391240e58f910d3d6b15f81c
Source dataset
uspto-grants-2012_01
Patent number
US08101613B2

Reaction notes

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