Triphenylphosphine → HCID 21069972, compound

HRID 1726661Notes

Reaction equation

HRID 1726661 reaction equation
[F:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][NH:7][C:8]([C:10]2[N:11]=[C:12]3[N:17]([C:18](=[O:28])[C:19]=2[O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:16][CH2:15][O:14][C:13]3([CH3:30])[CH3:29])=[O:9])=[C:4](I)[CH:3]=1.C(N(CC)C(C)C)(C)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[P:62]([O-:67])([O:65]C)[O:63][CH3:64]>C(#N)C.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:21]([O:20][C:19]1[C:18](=[O:28])[N:17]2[C:12]([C:13]([CH3:30])([CH3:29])[O:14][CH2:15][CH2:16]2)=[N:11][C:10]=1[C:8]([NH:7][CH2:6][C:5]1[CH:31]=[CH:32][C:2]([F:1])=[CH:3][C:4]=1[P:62](=[O:65])([OH:67])[O:63][CH3:64])=[O:9])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 81531DiisopropylethylamineHCID 21070019N-(4-fluoro-2-iodobenzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamideHCID 21884954Dimethylphosphite

Product 1

HCID 21069972HCID 21069972, compoundYield 64.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A solution of N-(4-fluoro-2-iodobenzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide (0.200 g, 0.35 mmol) in acetonitrile (5 ml) was flushed with argon and then treated with N,N-diisopropylethylamine (0.25 ml, 1.4 mmol), triphenylphosphine (0.030 g), palladium(II) acetate (0.040 g). and dimethyl phosphite (0.10 ml, 1.06 mmol). The reaction mixture was then heated in a microwave oven at 120° C. for 40 min. The reaction mixture was then diluted with ethyl acetate, washed with 0.1 N hydrochloric acid, brine, dried over anhydrous magnesium sulfate and concentrated. Purification of the residue by preparative HPLC (column YMC Pack C-18, 5μ, 20×250 mm, elution gradient acetonitrile-water 0.1% trifluoroacetic acid) gave 0.120 g (64% yield) of the title material as a white solid. 1HNMR 400 MHz (CDCl3) δ (ppm): 1.62 (6H, s, 2×CH3), 3.77 and 3.79 (3H, 2 s, OCH3), 3.95-4.05 (4H, m, 2×CH2), 4.75 (2H, d, J=4.6 Hz, NCH2), 5.32 (2H, s, OCH2), 7.22 (1H, m, aromatic), 7.3-7.35 (3H, m, aromatics), 7.38-7.42 (2H, m, aromatics), 7.48-7.54 (1H, m, aromatic), 7.55-7.62 (1H, m, aromatic), 8.54 (1H, broad t, NH). HRMS (ESI+) calculated for C25H28FN3O7P [M+H+]: 532.1649; found: 532.1642.

Workup

  1. washwashed with 0.1 N hydrochloric acid, brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. concentrationconcentrated
  4. customPurification of the residue
  5. washby preparative HPLC (column YMC Pack C-18, 5μ, 20×250 mm, elution gradient acetonitrile-water 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-bee55345e0f04d219d11ff99d446be61
Source dataset
uspto-grants-2009_02
Patent number
US07491819B1

Reaction notes

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