Tert-butyldimethyl((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-en-1-yl)oxy)silane → N-Butyl-7-(4-(tert-butyldimethylsilyloxy)cyclohex-1-enyl)-5-(4-fluorophenyl)-5H-pyrrolo[3,2-d]pyrimidin-2-amine

HRID 920665Notes

Reaction equation

HRID 920665 reaction equation
Br[C:2]1[C:6]2[N:7]=[C:8]([NH:11][CH2:12][CH2:13][CH2:14][CH3:15])[N:9]=[CH:10][C:5]=2[N:4]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[CH:3]=1.[C:23]([Si:27]([CH3:45])([CH3:44])[O:28][CH:29]1[CH2:34][CH2:33][C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31][CH2:30]1)([CH3:26])([CH3:25])[CH3:24].P(=O)([O-])[O-].[K+].[K+]>C1COCC1.O.CCOC(C)=O.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>[CH2:12]([NH:11][C:8]1[N:9]=[CH:10][C:5]2[N:4]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[CH:3]=[C:2]([C:32]3[CH2:33][CH2:34][CH:29]([O:28][Si:27]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:44])[CH3:45])[CH2:30][CH:31]=3)[C:6]=2[N:7]=1)[CH2:13][CH2:14][CH3:15]

Participants

8

Reactant 3

HCID 53393368Tert-butyldimethyl((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-en-1-yl)oxy)silaneHCID 867311567-Bromo-N-butyl-5-(4-fluorophenyl)-5H-pyrrolo[3,2-d]pyrimidin-2-amineHCID 178527066HCID 178527066, compound

Product 1

HCID 86731157N-Butyl-7-(4-(tert-butyldimethylsilyloxy)cyclohex-1-enyl)-5-(4-fluorophenyl)-5H-pyrrolo[3,2-d]pyrimidin-2-amineYield 83%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 7-bromo-N-butyl-5-(4-fluorophenyl)-5H-pyrrolo[3,2-d]pyrimidin-2-amine (0.11 g, 0.3 mmol), tert-butyldimethyl(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-enyloxy)silane (0.15 g, 0.45 mmol), potassium phosphonate (0.083 g, 0.60 mmol), tetrakis(triphenylphosphine)palladium (0.035 g, 0.03 mmol) in THF (4 mL) and water (1 mL) was stirred at room temperature for 1 min, then was heat at 150° C. for 1 h under microwave irradiation. The reaction mixture was diluted with EtOAc and washed with water. The aqueous layer was extracted with EtOAc (3×). The combined organic layer was dried (Na2SO4), concentrated, and purified by ISCO to provide the desired product (0.12 g, 83%). 1H NMR (400 MHz, CDCl3) δ 8.48 (s, 1H), 7.41-7.34 (m, 2H), 7.32 (s, 1H), 7.20 (t, J=8.5 Hz, 2H), 7.17-7.12 (m, 1H), 4.97 (t, J=5.6 Hz, 1H), 4.09-3.95 (m, 1H), 3.49 (dd, J=13.3, 6.5 Hz, 2H), 2.68-2.44 (m, 3H), 2.35-2.23 (m, 1H), 2.03-1.94 (m, 1H), 1.86-1.74 (m, 1H), 1.72-1.59 (m, 2H), 1.52-1.39 (m, 2H), 0.97 (t, J=7.3 Hz, 3H), 0.92 (s, 9H), 0.10 (s, 6H); MS m/z 495.3 [M+H]+.

Workup

  1. temperaturewas heat at 150° C. for 1 h under microwave irradiation
  2. washwashed with water
  3. extractionThe aqueous layer was extracted with EtOAc (3×)
  4. dry with materialThe combined organic layer was dried (Na2SO4)
  5. concentrationconcentrated
  6. custompurified by ISCO

Sources & evidence

ORD record
ord-86b4d92ef1aa4782b7437f7c521f70e6
Source dataset
uspto-grants-2016_03
Patent number
US09273056B2

Reaction notes

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