Triphenylphosphine → methyl (5-{3-[(2-chloro-5-fluoro-4-pyrimidinyl)(methyl)amino]propoxy}-1H-indol-1-yl)acetate

HRID 2424987Notes

Reaction equation

HRID 2424987 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([N:8]([CH3:13])[CH2:9][CH2:10][CH2:11][OH:12])[C:5]([F:14])=[CH:4][N:3]=1.[CH3:15][O:16][C:17](=[O:29])[CH2:18][N:19]1[C:27]2[C:22](=[CH:23][C:24](O)=[CH:25][CH:26]=2)[CH:21]=[CH:20]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>ClCCl.CCOC(C)=O>[CH3:15][O:16][C:17](=[O:29])[CH2:18][N:19]1[C:27]2[C:22](=[CH:23][C:24]([O:12][CH2:11][CH2:10][CH2:9][N:8]([C:6]3[C:5]([F:14])=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=3)[CH3:13])=[CH:25][CH:26]=2)[CH:21]=[CH:20]1

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 20770839methyl (5-hydroxy-1H-indol-1-yl)acetateHCID 578455183-[(2-Chloro-5-fluoro-4-pyrimidinyl)(methyl)amino]-1-propanol

Product 1

HCID 57992217methyl (5-{3-[(2-chloro-5-fluoro-4-pyrimidinyl)(methyl)amino]propoxy}-1H-indol-1-yl)acetateYield 56.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-[(2-chloro-5-fluoro-4-pyrimidinyl)(methyl)amino]-1-propanol (Example 83, 0.60 g, 2.73 mmol) and methyl(5-hydroxy-1H-indol-1-yl)acetate (Example 9, 0.37 g, 1.82 mmol) in dichloromethane (9 mL) was added triphenylphosphine (0.70 g, 2.73 mmol) and 1,1′-(azodicarbonyl)-dipiperidine (0.72 g, 2.73 mmol) under argon. The golden yellow mixture was stirred at rt for 18 h. The desired product (0.42 g, 56%) was obtained after column chromatography (67% hexanes in EtOAc). 1H NMR (300 MHz, CD2Cl2) δ 7.85 (d, 1H), 7.15-7.07 (m, 3H), 6.88-6.83 (m, 1H), 6.47-6.46 (m, 1H), 4.85 (s, 2H), 4.07 (t, 2H), 3.84 (t, 2H), 3.76 (s, 3H), 3.26 (d, 3H), 2.20-2.13 (m, 2H).

Sources & evidence

ORD record
ord-1890d1a7191848f8b10c85bb1d72d700
Source dataset
uspto-grants-2011_06
Patent number
US07964622B2

Reaction notes

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