2-Thiophenecarboxylic acid → HCID 11489938, compound

HRID 1174406Notes

Reaction equation

HRID 1174406 reaction equation
N=C=N.[S:4]1[CH:8]=[CH:7][CH:6]=[C:5]1[C:9]([OH:11])=O.O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[NH2:32][C@@H:33]([CH2:64][C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1)[CH2:34][C@H:35]([OH:63])[C@@H:36]([NH:50][C:51]([C@@H:53]([NH:58][C:59](=[O:62])[O:60][CH3:61])[C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:37][C:38]1[CH:43]=[CH:42][C:41](C2C=CC=CN=2)=[CH:40][CH:39]=1>CC(N(C)C)=O.C(#N)C.CO>[CH2:37]([C@H:36]([NH:50][C:51]([C@@H:53]([NH:58][C:59](=[O:62])[O:60][CH3:61])[C:54]([CH3:56])([CH3:57])[CH3:55])=[O:52])[C@@H:35]([OH:63])[CH2:34][C@@H:33]([NH:32][C:9]([C:5]1[S:4][CH:8]=[CH:7][CH:6]=1)=[O:11])[CH2:64][C:65]1[CH:66]=[CH:67][CH:68]=[CH:69][CH:70]=1)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1

Participants

9

Reactant 5

HCID 107002-Thiophenecarboxylic acidHCID 81531DiisopropylethylamineHCID 160435CarbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 42625793methyl (1S)-1-[({(1S,2S,4S)-4-amino-2-hydroxy-5-phenyl-1-[4-(2-pyridinyl)benzyl]pentyl}amino)carbonyl]-2,2-dimethylpropylcarbamate

Product 1

HCID 11489938HCID 11489938, compoundYield 38.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent3×HCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

A Smith Process Vial (2-5 mL) was charged with a stir bar and PS-Carbodiimide resin (108 mg, 0.12 mmol.). To the vessel were added thiophene-2-carboxylic acid (5.6 mg, 0.044 mmol.) d in 0.2 mL dimethyl acetamide, 1-hydroxybenzotriazole hydrate (5.4 mg, 0.04 mmol.) in 0.5 mL acetonitrile (acetonitrile), diisopropylethylamine (16.7 mg, 0.12 mmol.) in 0.5 mL acetonitrile and the product of Example 23S (19.6 mg, 0.04 mmol.) in 0.7 mL acetonitrile. The reaction vessel was sealed and heated to 100° C. for 300 seconds in an Ermys Optimizer. After cooling the reaction mixture was transferred to a pre-packed 1 g column of Si-Carbonate (>4 eq. of functionalized reagent), which had been previously conditioned with methanol. The reaction products were collected, and the solvents were evaporated. The crude residue was dissolved in 1:1 dimethyl sulfoxide/methanol and purified by reverse phase HPLC to give 8.7 mg (35%) of the title compound. 1H NMR (500 MHz, DMSO-d6) δ ppm 0.83 (s, 9 H), 1.55-1.76 (m, 2 H), 2.64-2.83 (m, 4 H), 3.55 (s, 3 H), 3.60 (t, J=6.26 Hz, 1 H), 3.88 (s, 1 H), 4.18 (d, J=7.63 Hz, 1 H), 4.29 (s, 1 H), 7.01-7.25 (m, 12 H), 7.54 (d, J=8.85 Hz, 1 H), 7.60 (d, J=3.66 Hz, 1 H), 7.66-7.68 (m, 1 H), 8.18 (d, J=8.85 Hz, 1 H).

Workup

  1. additionA Smith Process Vial (2-5 mL) was charged with a stir bar
  2. customThe reaction vessel was sealed
  3. temperatureAfter cooling the reaction mixture
  4. customThe reaction products were collected
  5. customthe solvents were evaporated
  6. dissolutionThe crude residue was dissolved in 1:1 dimethyl sulfoxide/methanol
  7. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-bcd657fa258d4840bd4530a2b5dbc4ae
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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