Diphosgene → (S)-1-(2-(tert-butyldimethylsilyloxy)ethyl)-4-isopropyl-3-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)imidazolidin-2-one

HRID 539017Notes

Reaction equation

HRID 539017 reaction equation
[Si:1]([O:8][CH2:9][CH2:10][NH:11][CH2:12][C@@H:13]([NH:17][C:18]1[CH:23]=[CH:22][N:21]2[N:24]=[CH:25][C:26]([C:27]3[CH:32]=[CH:31][C:30]([C:33]4[N:34]([CH2:38][O:39][CH2:40][CH2:41][Si:42]([CH3:45])([CH3:44])[CH3:43])[CH:35]=[CH:36][N:37]=4)=[CH:29][CH:28]=3)=[C:20]2[N:19]=1)[CH:14]([CH3:16])[CH3:15])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.Cl[C:56](OC(Cl)(Cl)Cl)=[O:57]>ClCCl>[Si:1]([O:8][CH2:9][CH2:10][N:11]1[CH2:12][C@H:13]([CH:14]([CH3:16])[CH3:15])[N:17]([C:18]2[CH:23]=[CH:22][N:21]3[N:24]=[CH:25][C:26]([C:27]4[CH:28]=[CH:29][C:30]([C:33]5[N:34]([CH2:38][O:39][CH2:40][CH2:41][Si:42]([CH3:44])([CH3:45])[CH3:43])[CH:35]=[CH:36][N:37]=5)=[CH:31][CH:32]=4)=[C:20]3[N:19]=2)[C:56]1=[O:57])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 10426DiphosgeneHCID 81531DiisopropylethylamineHCID 68088943(S)-N1-(2-(tert-butyldimethylsilyloxy)ethyl)-3-methyl-N2-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)butane-1,2-diamine

Product 1

HCID 67034424(S)-1-(2-(tert-butyldimethylsilyloxy)ethyl)-4-isopropyl-3-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)imidazolidin-2-oneYield 40.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of (S)—N1-(2-(tert-butyldimethylsilyloxy)ethyl)-3-methyl-N2-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)butane-1,2-diamine (0.055 mmol) in dichloromethane (1 mL) was added diisopropylethylamine (0.019 mL, 0.14 mmol). Trichloromethyl chloroformate (0.010 mL, 0.083 mmol) was added dropwise at 0° C. under N2. The reaction mixture was stirred at 0° C. for 30 minutes, then diluted with dichloromethane, washed with aqueous saturated NaHCO3 and brine, dried and concentrated. The residue was purified by silica gel chromatography (dichloromethane:MeOH, 100:1) to give (S)-1-(2-(tert-butyldimethylsilyloxy)ethyl)-4-isopropyl-3-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)imidazolidin-2-one (15 mg, 40% for two steps). LCMS (APCI+) m/z 676.9 [M+H]

Workup

  1. washwashed with aqueous saturated NaHCO3 and brine
  2. customdried
  3. concentrationconcentrated
  4. customThe residue was purified by silica gel chromatography (dichloromethane:MeOH, 100:1)

Sources & evidence

ORD record
ord-ddb397a0c16e4908a3c3a8074e8bd1c0
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

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