Diisopropylethylamine → Tert-butyl 4-(4-(1-(di-tert-butoxyphosphoryloxy)-2-phenylpropan-2-ylcarbamoyl)-2-(7-isopropylpyrido[2,3-d]pyrimidin-4-ylamino)phenylthio)phenylcarbamate

HRID 605409Notes

Reaction equation

HRID 605409 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([S:15][C:16]2[CH:24]=[CH:23][C:19]([C:20](O)=[O:21])=[CH:18][C:17]=2[NH:25][C:26]2[C:27]3[CH:35]=[CH:34][C:33]([CH:36]([CH3:38])[CH3:37])=[N:32][C:28]=3[N:29]=[CH:30][N:31]=2)=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[P:61]([O:79][C:80]([CH3:83])([CH3:82])[CH3:81])([O:74][C:75]([CH3:78])([CH3:77])[CH3:76])([O:63][CH2:64][C:65]([NH2:73])([C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1)[CH3:66])=[O:62].C(N(CC)C(C)C)(C)C>CS(C)=O.O>[C:80]([O:79][P:61]([O:63][CH2:64][C:65]([NH:73][C:20]([C:19]1[CH:23]=[CH:24][C:16]([S:15][C:12]2[CH:13]=[CH:14][C:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[CH:10][CH:11]=2)=[C:17]([NH:25][C:26]2[C:27]3[CH:35]=[CH:34][C:33]([CH:36]([CH3:37])[CH3:38])=[N:32][C:28]=3[N:29]=[CH:30][N:31]=2)[CH:18]=1)=[O:21])([C:67]1[CH:68]=[CH:69][CH:70]=[CH:71][CH:72]=1)[CH3:66])([O:74][C:75]([CH3:78])([CH3:76])[CH3:77])=[O:62])([CH3:81])([CH3:82])[CH3:83]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 593768924-(4-tert-Butoxycarbonylamino-phenylsulfanyl)-3-(7-isopropyl-pyrido[2,3-d]pyrimidin-4-ylamino)-benzoic acidHCID 670410332-Amino-2-phenylpropyl di-tert-butyl phosphate

Product 1

HCID 67040563Tert-butyl 4-(4-(1-(di-tert-butoxyphosphoryloxy)-2-phenylpropan-2-ylcarbamoyl)-2-(7-isopropylpyrido[2,3-d]pyrimidin-4-ylamino)phenylthio)phenylcarbamateYield 69%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

The product of Example 385E (100 mg, 0.19 mmol), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate [TBTU] (79 mg, 0.24 mmol) and the product of Example 442C (90 mg., 0.26 mmol) in DMSO (1.0 mL) were treated with N,N-diisopropylethylamine (100 μL, 0.57 mmol) dropwise at room temperature and stirred under N2 for 2 hours. The reaction was diluted with WATER (10 mL) with stirring. The resulting precipitate was extracted with ethyl acetate (50 mL). The organic layer was washed with WATER (3×), saturated aqueous NaHCO3, then brine, dried over MgSO4, and concentrated. The residue was purified by silica gel column chromatography (ethyl acetate:chloroform=4:1) to give the title compound as a pale yellow amorphous solid (112 mg, 69%).

Workup

  1. stirringwith stirring
  2. extractionThe resulting precipitate was extracted with ethyl acetate (50 mL)
  3. washThe organic layer was washed with WATER (3×), saturated aqueous NaHCO3
  4. dry with materialbrine, dried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column chromatography (ethyl acetate:chloroform=4:1)

Sources & evidence

ORD record
ord-d37ba02521fc4a51982ba18598574533
Source dataset
uspto-grants-2011_03
Patent number
US07910595B2

Reaction notes

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