Trifluoroacetic acid → HCID 178525667, compound

HRID 909922Notes

Reaction equation

HRID 909922 reaction equation
C([N:4]1[CH:8]=[C:7]([C:9]2[CH:10]=[C:11]([CH:57]=[CH:58][CH:59]=2)[CH2:12][CH2:13][O:14][CH2:15][CH2:16][C:17]([N:19]([CH2:26][CH2:27][N:28]([CH2:36][CH2:37][C:38]2[C:43]3[O:44][CH2:45][C:46](=[O:48])[NH:47][C:42]=3[C:41]([O:49]C(OC(C)(C)C)=O)=[CH:40][CH:39]=2)C(=O)OC(C)(C)C)[CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)=[O:18])[N:6]=[N:5]1)C=C.CN1C(=O)CC(=O)N(C)C1=O.[C:71]([OH:77])([C:73]([F:76])([F:75])[F:74])=[O:72]>C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:74][C:73]([F:76])([F:75])[C:71]([OH:77])=[O:72].[NH:4]1[CH:8]=[C:7]([C:9]2[CH:10]=[C:11]([CH:57]=[CH:58][CH:59]=2)[CH2:12][CH2:13][O:14][CH2:15][CH2:16][C:17]([N:19]([CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)[CH2:26][CH2:27][NH:28][CH2:36][CH2:37][C:38]2[C:43]3[O:44][CH2:45][C:46](=[O:48])[NH:47][C:42]=3[C:41]([OH:49])=[CH:40][CH:39]=2)=[O:18])[N:6]=[N:5]1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 69860Dimethylbarbituric acidHCID 68237520HCID 68237520, compound

Product 1

HCID 178525667HCID 178525667, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

tert-Butyl 2-(3-(3-(1-allyl-1H-1,2,3-triazol-4-yl)phenethoxy)-N-cyclohexylpropanamido)ethyl(2-(5-(tert-butoxycarbonyloxy)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)ethyl)carbamate [Example 14, Step iv)] (220 mg), 1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione (126 mg) and tetrakis(triphenylphosphine)palladium(0) (31 mg) were dissolved in DCM (2 mL) and sealed into a microwave tube. The reaction was heated to 100° C., over a period of 90 min in the microwave reactor. After cooling to room temperature, TFA (1 mL) was added and the mixture was stirred for 30 min, then concentrated. The crude product was purified by preparative HPLC on a Phenomenex Gemini column using a gradient of aqueous 0.1% trifluoroacetic acid in acetonitrile as eluent to afford the titled compound (63.5 mg) as a solid. MS [M+H]+=577.3 (calc=577.3138) (MultiMode+) 1H NMR (400 MHz, CD3OD) δ 8.12 (s, 1H), 7.71 (s, 1H), 7.63 (d, J=7.8 Hz, 1H), 7.33 (t, J=7.5 Hz, 1H), 7.21 (d, J=8.0 Hz, 1H), 6.69 (d, J=8.2 Hz, 1H), 6.47 (d, J=8.5 Hz, 1H), 4.61 (s, 2H), 3.72 (t, J=6.7 Hz, 2H), 3.72 (t, J=5.9 Hz, 2H), 3.71-3.63 (m, 1H), 3.47 (t, J=6.9 Hz, 2H), 3.11 (t, J=7.2 Hz, 2H), 3.02 (t, J=5.7 Hz, 2H), 2.89 (t, J=6.7 Hz, 2H), 2.87 (t, J=7.1 Hz, 2H), 2.62 (t, J=6.0 Hz, 2H), 1.80-1.72 (m, 2H), 1.69-1.58 (m, 3H), 1.46-1.24 (m, 4H), 1.16-1.05 (m, 1H).

Workup

  1. customsealed into a microwave tube
  2. temperatureAfter cooling to room temperature
  3. concentrationconcentrated
  4. customThe crude product was purified by preparative HPLC on a Phenomenex Gemini column

Sources & evidence

ORD record
ord-86821fc4ba9d499b9820b5dfc19e258b
Source dataset
uspto-grants-2011_09
Patent number
US08017602B2

Reaction notes

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