Diisopropylethylamine → (R)-benzyl 3-hydroxy-1-(4-(2-(4-morpholino-phenylamino)pyrimidin-4-yl)phenylamino)-1-oxopropan-2-ylcarbamate

HRID 2091965Notes

Reaction equation

HRID 2091965 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]3[CH:20]=[CH:19][C:18]([N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)=[CH:17][CH:16]=3)[N:9]=2)=[CH:4][CH:3]=1.[C:27]([NH:37][C@@H:38]([C:41](O)=[O:42])[CH2:39][OH:40])([O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:28].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CC(N(C)C)=O.CO.C(Cl)Cl.O>[OH:42][CH2:41][C@@H:38]([NH:37][C:27](=[O:28])[O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C:39]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]3[CH:16]=[CH:17][C:18]([N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)=[CH:19][CH:20]=3)[N:9]=2)=[CH:4][CH:3]=1)=[O:40]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 489184Z-D-Ser-OHHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 248780154-(4-aminophenyl)-N-(4-morpholinophenyl)pyrimidin-2-amine

Product 1

HCID 70271434(R)-benzyl 3-hydroxy-1-(4-(2-(4-morpholino-phenylamino)pyrimidin-4-yl)phenylamino)-1-oxopropan-2-ylcarbamateYield 78.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 31374DimethylacetamideSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

To a solution of 4-(4-aminophenyl)-N-(4-morpholinophenyl)pyrimidin-2-amine 249(a) (521 mg, 1.5 mmol), N-CBZ-D-Serine (359 mg, 1.5 mmol), and DIEA (0.653 mL, 3.75 mol) in DMA (4 mL) was added HATU (855 mg, 2.25 mmol) and the solution was stirred at room temperature for 0.5 hour. Excess H2O was added to the reaction mixture. The precipitate was collected and were redissolved in CH2Cl2, washed with NaHCO3 (aq) (2×), brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by silica column chromatography. (1% MeOH/DCM as eluent) to afford (R)-benzyl 3-hydroxy-1-(4-(2-(4-morpholino-phenylamino)pyrimidin-4-yl)phenylamino)-1-oxopropan-2-ylcarbamate 365(a) (668 mg, 78% yield).

Workup

  1. customThe precipitate was collected
  2. dissolutionwere redissolved in CH2Cl2
  3. washwashed with NaHCO3 (aq) (2×), brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica column chromatography

Sources & evidence

ORD record
ord-e83eac2661b7407188877f9bf35b7344
Source dataset
uspto-grants-2013_05
Patent number
US08440663B2

Reaction notes

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