Triethylamine → HCID 53984519, compound

HRID 987532Notes

Reaction equation

HRID 987532 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:20][C:21]([OH:23])=O)[CH:6]=[CH:7][C:8]=1[NH:9][C:10]([NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:19])=[O:11].[C:24]([O:28][C:29]([N:31]1[C:40]2[C:35](=[CH:36][CH:37]=[C:38]([CH:41]([CH3:48])[CH2:42][C:43]([O:45][CH2:46][CH3:47])=[O:44])[CH:39]=2)[NH:34][CH2:33][CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25].C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>O1CCCC1>[C:24]([O:28][C:29]([N:31]1[C:40]2[C:35](=[CH:36][CH:37]=[C:38]([CH:41]([CH3:48])[CH2:42][C:43]([O:45][CH2:46][CH3:47])=[O:44])[CH:39]=2)[N:34]([C:21](=[O:23])[CH2:20][C:5]2[CH:6]=[CH:7][C:8]([NH:9][C:10]([NH:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[CH3:19])=[O:11])=[C:3]([O:2][CH3:1])[CH:4]=2)[CH2:33][CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 114498403-Methoxy-4-o-tolylureidophenylacetic acid2×HCID 53851036HCID 53851036, compound

Product 1

HCID 53984519HCID 53984519, compoundYield 51.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of [3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetic acid (0.536 g) and 7-(2-ethoxycarbonyl-1-methyl-ethyl)-3,4-dihydro-2H-quinoxaline-1-carboxylic acid tert-butyl ester (396 mg, Reference Example 19) in tetrahydrofuran (10 ml) containing 4 Angström molecular sieves (0.5 g) was treated with triethyl amine (638 μl), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (518 mg) and 4-dimethyl-aminopyridin (14 mg). After stirring for 5 hours further aliquots of [3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetic acid (0.178 g) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (172 mg) were added and stirring was continued for a further 18 hours. The reaction mixture was filtered through a celite and the filter pad was washed with ethyl acetate (50 ml). The combined filtrate and washings were washed three times with aqueous saturated ammonium chloride (20 ml), then dried over magnesium sulfate and then evaporated (40° C., 40 mbar). The residue (1.2 g) was submitted to chromatography (36 g silica, 0.040-0.063 mm particle size) eluting with a mixture of cyclohexane and ethyl acetate (70:30, v/v) to afford the title compound as a white powder (379 mg). TLC: RF=15/65 (cyclohexane:ethyl acetate, 1:1). 1H NMR (400 HMz, (CD3)2SO, at room temperature, we observe a mixture of rotamers): δ1.14 (t, J=7 Hz, 31); 1.24 (d, J=7 Hz, 3H); 1.48 (s, 9 H); 2.26 (s, 3H); 2.58 (d, J=7.5 Hz, 2H); 3.17 (m, 1H); 3.64 (m, 2H); from 3.75 to 3.90 (m, 7H); 4.04 (q, J=7 Hz, 2H); from 6.55 to 6.85 (very broad band, 2H); 6.96 (t, J=7.5 Hz, 1H); 7.00 (broad d, J=8 Hz, 1H); from 7.10 to 7.20 (m, 2H); 7.46 (broad band, 1H); 7.64 (broad s, 1H); 7.78 (d, J=8 Hz, 1H); 8.01 (d, J=8 Hz, 1H); 8.48 (s, 1H); 8.54 (broad s, 1H). MS (EI): 644 (M+).

Workup

  1. additioncontaining 4 Angström molecular sieves (0.5 g)
  2. additionwere added
  3. filtrationThe reaction mixture was filtered through a celite
  4. washthe filter pad was washed with ethyl acetate (50 ml)
  5. washThe combined filtrate and washings were washed three times with aqueous saturated ammonium chloride (20 ml)
  6. dry with materialdried over magnesium sulfate
  7. customevaporated (40° C., 40 mbar)
  8. washeluting with a mixture of cyclohexane and ethyl acetate (70:30, v/v)

Sources & evidence

ORD record
ord-ffd57340d7344404b8bbede09117acaa
Source dataset
uspto-grants-2003_10
Patent number
US06632814B1

Reaction notes

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