Trifluoroacetic acid → HCID 67076124, compound

HRID 909925Notes

Reaction equation

HRID 909925 reaction equation
C([N:4]1[N:8]=[N:7][C:6]([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: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].[N:7]1[NH:8][N:4]=[N:5][C:6]=1[C:9]1[CH:10]=[C:11]([CH:57]=[CH:58][CH:59]=1)[CH2:12][CH2:13][O:14][CH2:15][CH2:16][C:17]([N:19]([CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1)[CH2:26][CH2:27][NH:28][CH2:36][CH2:37][C:38]1[C:43]2[O:44][CH2:45][C:46](=[O:48])[NH:47][C:42]=2[C:41]([OH:49])=[CH:40][CH:39]=1)=[O:18]

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 69860Dimethylbarbituric acidHCID 68237525HCID 68237525, compound

Product 1

HCID 67076124HCID 67076124, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

tert-Butyl 2-(3-(3-(2-allyl-2H-tetrazol-5-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 15, Step v)] (170 mg), 1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione (97 mg) and tetrakis(triphenylphosphine)palladium(0) (24 mg, 0.02 mmol) were dissolved in DCM (2 mL) and sealed into a microwave tube. The reaction was heated to 100° C., over a period of 30 min in the microwave reactor. After cooling to rt, TFA (1 mL) was added and the mixture stirred for 30 min. The mixture was concentrate in vacuo do give a crude product. 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 (41.8 mg) as a solid. MS [M+H]+=578.3 (calc=578.3091) (MultiMode+) 1H NMR (400 MHz, CD3OD) δ 7.92 (s, 1H), 7.80 (dt, J=1.6 and 7.4 Hz, 1H), 7.47 (t, J=7.5 Hz, 1H), 7.44 (dt, J=1.5 and 7.9 Hz, 1H), 6.70 (d, J=8.5 Hz, 1H), 6.46 (d, J=8.2 Hz, 1H), 4.61 (s, 2H), 3.74 (t, J=6.5 Hz, 2H), 3.72 (t, J=6.0 Hz, 2H), 3.71-3.63 (m, 1H), 3.48 (t, J=5.8 Hz, 2H), 3.14 (t, J=7.1 Hz, 2H), 3.04 (t, J=5.7 Hz, 2H), 2.94 (t, J=6.3 Hz, 2H), 2.87 (t, J=7.0 Hz, 2H), 2.63 (t, J=6.0 Hz, 2H), 1.79-1.71 (m, 2H), 1.68-1.57 (m, 3H), 1.44-1.23 (m, 4H), 1.16-1.03 (m, 1H)

Workup

  1. customsealed into a microwave tube
  2. temperatureAfter cooling to rt
  3. concentrationThe mixture was concentrate in vacuo
  4. customdo give a crude product
  5. customThe crude product was purified by preparative HPLC on a Phenomenex Gemini column

Sources & evidence

ORD record
ord-642aa7ac6d92481485608de228fd4409
Source dataset
uspto-grants-2011_09
Patent number
US08017602B2

Reaction notes

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