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

HRID 603492Notes

Reaction equation

HRID 603492 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][CH2:11][OH:12])[C:5]([Cl:13])=[CH:4][N:3]=1.O[C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[C@H:20]([CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:19][CH2:18]2.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1CCN(C(N=NC(N2CCCCC2)=O)=O)CC1>C1COCC1>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][CH2:11][O:12][C:15]2[CH:16]=[C:17]3[C:21](=[CH:22][CH:23]=2)[C@H:20]([CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:19][CH2:18]3)[C:5]([Cl:13])=[CH:4][N:3]=1

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 593004183-[(2,5-Dichloro-4-pyrimidinyl)amino]-1-propanol

Product 1

HCID 59300519ethyl ((1S)-5-{3-[(2,5-dichloro-4-pyrimidinyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetateYield 89%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-[(2-chloro-5-chloro-4-pyrimidinyl)amino]-1-propanol (Example 440, 1.08 g, 4.90 mmol) and ethyl [(1S)-5-hydroxy-2,3-dihydro-1H-inden-1-yl]acetate (Example 6, 539 mg, 2.45 mmol) in THF (40 mL) were added PPh3 (1.29 g, 4.90 mmol) and ADDP (1.26 g, 4.90 mmol). The reaction mixture was vigorously stirred at rt for 72 h, after which additional amounts of PPh3 (1.29 g, 4.90 mmol) and ADDP (1.26 g, 4.90 mmol) were added. After stirring for 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 (1:1 hexanes/EtOAc) to give the product (920 mg, 89%). 1H NMR (400 MHz, CDCl3): δ 1.29 (t, 3H), 1.71-1.82 (m, 1H), 2.15 (qt, 2H), 2.35-2.47 (m, 2H), 2.72 (dd, 1H), 2.79-2.98 (m, 2H), 3.48-3.58 (m, 1H), 3.74 (q, 2H), 4.12 (t, 2H), 4.18 (q, 2H), 6.22-6.31 (b, 1H), 6.73 (dd, 1H), 6.79 (d, 1H), 7.08 (d, 1H), 7.25 (s, 1H).

Workup

  1. stirringAfter stirring for 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 (1:1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-67eda978a91947c084597f6ebb78c94f
Source dataset
uspto-grants-2011_03
Patent number
US07906653B2

Reaction notes

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