Diisopropylethylamine → Ethyl 2-(4-(4-(tert-butoxycarbonylamino)phenylthio)-3-(7-isopropylpyrido[2,3-d]pyrimidin-4-ylamino)benzamido)-2-phenylpropanoate

HRID 605410Notes

Reaction equation

HRID 605410 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.[NH2:61][C:62]([C:69]1[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=1)([CH3:68])[C:63]([O:65][CH2:66][CH3:67])=[O:64].C(N(CC)C(C)C)(C)C>CS(C)=O.O>[C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[CH:11][C:12]([S:15][C:16]2[CH:24]=[CH:23][C:19]([C:20]([NH:61][C:62]([C:69]3[CH:70]=[CH:71][CH:72]=[CH:73][CH:74]=3)([CH3:68])[C:63]([O:65][CH2:66][CH3:67])=[O:64])=[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:13][CH:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 3571202Ethyl 2-amino-2-phenylpropanoateHCID 593768924-(4-tert-Butoxycarbonylamino-phenylsulfanyl)-3-(7-isopropyl-pyrido[2,3-d]pyrimidin-4-ylamino)-benzoic acid

Product 1

HCID 67040905Ethyl 2-(4-(4-(tert-butoxycarbonylamino)phenylthio)-3-(7-isopropylpyrido[2,3-d]pyrimidin-4-ylamino)benzamido)-2-phenylpropanoateYield 78%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

The product of Example 385E (90 mg, 0.17 mmol), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate [TBTU] (60 mg, 0.19 mmol) and ethyl 2-amino-2-phenylpropanoate (39 mg., 0.20 mmol) in DMSO (0.9 mL) was reacted with N,N-diisopropylethylamine (0.060 mL, 0.34 mmol) dropwise at room temperature then stirred at room temperature for 18 hours under N2. The mixture was poured into water (10 mL) with stirring. The resulting precipitate was extracted with ethyl acetate (50 mL) and 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 chromatography (ethyl acetate:chloroform 4:1) to give the title compound as a pale yellow amorphous solid (93 mg, 78%).

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 chromatography (ethyl acetate:chloroform 4:1)

Sources & evidence

ORD record
ord-f82061a7bcee4df588651382d9c7f1c7
Source dataset
uspto-grants-2011_03
Patent number
US07910595B2

Reaction notes

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