Triphenylphosphine → ethyl ((1S)-5-{3-[(2-chloro-5-methyl-4-pyrimidinyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

HRID 2235954Notes

Reaction equation

HRID 2235954 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][CH2:11][OH:12])[C:5]([CH3:13])=[CH:4][N:3]=1.[CH2:14]([O:16][C:17](=[O:29])[CH2:18][C@H:19]1[C:27]2[C:22](=[CH:23][C:24](O)=[CH:25][CH:26]=2)[CH2:21][CH2:20]1)[CH3:15].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1CCN(C(N=NC(N2CCCCC2)=O)=O)CC1>C1COCC1>[CH2:14]([O:16][C:17](=[O:29])[CH2:18][C@H:19]1[C:27]2[C:22](=[CH:23][C:24]([O:12][CH2:11][CH2:10][CH2:9][NH:8][C:6]3[C:5]([CH3:13])=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=3)=[CH:25][CH:26]=2)[CH2:21][CH2:20]1)[CH3:15]

Participants

6

Reactant 4

HCID 11776Triphenylphosphine2×HCID 730421,1'-(Azodicarbonyl)dipiperidine2×HCID 16110404ethyl 2-[(1S)-5-hydroxy-2,3-dihydro-1H-inden-1-yl]acetateHCID 593004463-[(2-Chloro-5-methyl-4-pyrimidinyl)amino]-1-propanol

Product 1

HCID 59300503ethyl ((1S)-5-{3-[(2-chloro-5-methyl-4-pyrimidinyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetateYield 99%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-[(2-chloro-5-methyl-4-pyrimidinyl)amino]-1-propanol (Example 339, 1.77 g, 8.81 mmol) and ethyl[(1S)-5-hydroxy-2,3-dihydro-1H-inden-1-yl]acetate Example 6, 970 mg, 8.81 mmol) in THF (33 mL) were added PPh3 (2.31 g, 8.81 mmol) and ADDP (2.22 g, 8.81 mmol). The reaction mixture was vigorously stirred at rt for 24 h, after which additional amounts of PPh3 (2.31 g, 8.81 mmol) and ADDP (2.22 g, 8.81 mmol) were added. After an additional 24 h, the reaction mixture was diluted with hexanes, filtered through Celite®, and the filtrate concentrated under reduced pressure. The residue was then purified by silica gel chromatography (2:1 to 1:1 hexanes/EtOAc) to give the product (1.70 g, 99%). 1H NMR (400 MHz, CDCl3) δ 1.29 (t, 3H), 1.75-1.80 (m, 1H), 2.02 (s, 3H), 2.12-2.18 (m, 2H), 2.38-2.46 (m, 2H), 2.72 (dd, 1H), 2.84-2.2.92 (m, 2H), 3.52-3.55 (m, 1H), 3.73 (q, 2H), 4.13 (t, 2H), 4.18 (q, 2H), 6.70 (d, 1H), 6.77 (s, 1H), 7.08 (d, 1H), 7.78 (s, 1H).

Workup

  1. waitAfter an additional 24 h
  2. filtrationfiltered through Celite®
  3. concentrationthe filtrate concentrated under reduced pressure
  4. customThe residue was then purified by silica gel chromatography (2:1 to 1:1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-0bf1bba9cf8345c0bb5ad2a15650ffa8
Source dataset
uspto-grants-2010_05
Patent number
US07714004B2

Reaction notes

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