Diisopropyl Ether → HCID 67040380, compound

HRID 605334Notes

Reaction equation

HRID 605334 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)[C:48]2[CH:49]=[CH:50][CH:51]=[CH:52][C:47]=2N=N1.[CH:61]([N:64](CC)C(C)C)(C)[CH3:62].O(C(C)C)C(C)C>CS(C)=O.O>[C:1]([O:5][C:6](=[O:7])[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:21])[NH:64][C@H:61]([C:47]3[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=3)[CH3:62])=[CH:18][C:17]=2[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:11][CH:10]=1)([CH3:3])([CH3:4])[CH3:2]

Participants

7

Reactant 4

HCID 7914Diisopropyl EtherHCID 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 acid

Product 1

HCID 67040380HCID 67040380, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

To a suspension of 4-(4-tert-butoxycarbonylamino-phenylsulfanyl)-3-(7-isopropyl-pyrido[2,3-d]pyrimidin-4-ylamino)-benzoic acid (100 mg, 0.19 mmol) and O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate [TBTU] (68 mg, 0.21 mmol) in DMSO (1 mL) was added S-(−)-α-methylbenzylamine (25 μL, 0.19 mmol) and N,N-diisopropylethylamine (67 μL, 0.38 mmol) dropwise at room temperature under N2. The mixture was stirred at room temperature for 1 hour under N2, and then poured into H2O (20 mL) under stirring. The resulting precipitate was extracted with AcOEt (20 mL). The organic layer was washed with H2O (3 times) and 10% NaHCO3, dried over MgSO4, and evaporated to give yellow amorphous. The oily residue was separated by silica gel column chromatography (AcOEt/n-hexane=10/1) to give pale yellow amorphous, which was solidified by the treatment of i-Pr2O. The resulting solid was collected by filtration, washed with i-Pr2O, and dried at 40° C. for 3 days under reduced pressure to give the title compound as pale yellow crystal (92 mg, 77%). 1H-NMR (300 MHz, DMSO-d6) δ ppm: 1.33 (d, J=7.0 Hz, 6H), 1.45 (d, J=7.3 Hz, 3H), 1.47 (s, 9H), 3.22 (septet, J=7.0 Hz, 1H), 5.16 (quintet, J=7.3 Hz, 1H), 6.97 (d, J=8.4 Hz, 1H), 7.17-7.25 (m, 1H), 7.26-7.40 (m, 4H), 7.32 (d, J=8.8 Hz, 2H), 7.51 (d, J=8.8 Hz, 2H), 7.63 (d, J=8.5 Hz, 1H), 7.74 (br-d, J=8.4 Hz, 1H), 7.93 (br-s, 1H), 8.57 (s, 1H), 8.81 (d, J=7.3 Hz, 1H), 8.84 (d, J=8.5 Hz, 1H), 9.58 (s, 1H), 10.19 (s, 1H) MS ESI+ m/z: 635 (M+H)

Workup

  1. stirringunder stirring
  2. extractionThe resulting precipitate was extracted with AcOEt (20 mL)
  3. washThe organic layer was washed with H2O (3 times) and 10% NaHCO3
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. customto give yellow amorphous
  7. customThe oily residue was separated by silica gel column chromatography (AcOEt/n-hexane=10/1)
  8. customto give pale yellow amorphous
  9. filtrationThe resulting solid was collected by filtration
  10. washwashed with i-Pr2O
  11. customdried at 40° C. for 3 days under reduced pressure

Sources & evidence

ORD record
ord-24c263fe58214855abd2ab0a6dd49a87
Source dataset
uspto-grants-2011_03
Patent number
US07910595B2

Reaction notes

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