Citric Acid → HCID 67199379, compound

HRID 2421780Notes

Reaction equation

HRID 2421780 reaction equation
FC(F)(F)[C:3]([OH:5])=[O:4].C(O[C:13](=[O:63])[NH:14][CH2:15][CH2:16][C:17]([NH:19][CH2:20][CH2:21][CH2:22][N:23]([C@H:36]1[CH2:60][CH2:59][C@@:58]2([CH3:61])[C:38](=[CH:39][CH2:40][C@@H:41]3[C@@H:57]2[CH2:56][CH2:55][C@@:54]2([CH3:62])[C@H:42]3[CH2:43][CH2:44][C@@H:45]2[C@H:46]([CH3:53])[CH2:47][CH2:48][CH2:49][CH:50]([CH3:52])[CH3:51])[CH2:37]1)[S:24]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[N+:33]([O-:35])=[O:34])(=[O:26])=[O:25])=[O:18])(C)(C)C.[OH-].[Na+].[CH:66]([N:69](C(C)C)CC)(C)[CH3:67].C(O)(=O)[CH2:76][C:77]([CH2:82]C(O)=O)([C:79](O)=O)O>C(Cl)Cl.CO>[C:77]([O:5][C:3](=[O:4])[NH:69][CH2:66][CH2:67][C:13]([NH:14][CH2:15][CH2:16][C:17]([NH:19][CH2:20][CH2:21][CH2:22][N:23]([C@H:36]1[CH2:60][CH2:59][C@@:58]2([CH3:61])[C:38](=[CH:39][CH2:40][C@@H:41]3[C@@H:57]2[CH2:56][CH2:55][C@@:54]2([CH3:62])[C@H:42]3[CH2:43][CH2:44][C@@H:45]2[C@H:46]([CH3:53])[CH2:47][CH2:48][CH2:49][CH:50]([CH3:52])[CH3:51])[CH2:37]1)[S:24]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[N+:33]([O-:35])=[O:34])(=[O:26])=[O:25])=[O:18])=[O:63])([CH3:76])([CH3:79])[CH3:82]

Participants

8

Reactant 5

HCID 311Citric AcidHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 67196542HCID 67196542, compound

Product 1

HCID 67199379HCID 67199379, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
23 °C

Procedure

Trifluoroacetic acid in CH2Cl2 (2:25, 10 mL) was added to tert-butyl 3-[(3-{(3β)-cholest-5-en-3-yl[(2-nitrophenyl)sulfonyl]amino}propyl)amino]-3-oxopropylcarbamate (17) (50 mg, 0.062 mmol). After 1 h at 23° C., TLC analysis (MeOH/CH2Cl2b , 1:50) revealed conversion to the more polar primary amine. Aqueous NaOH (1 M, 20 mL) was added, the mixture was extracted with CH2Cl2 (2×5 mL), the combined organic extracts were dried over anhydrous Na2SO4, and solvent was removed in vacuo. Boc-β-alanine N-hydroxysuccinimidyl ester (54 mg, 0.189 mmol), CH2Cl2 (9 mL) and diisopropylethylamine (50 μL, 0.277 mmol) were added. After stirring for 5 h at 23° C., CH2Cl2 (5 mL) and aqueous citric acid (10%, 25 mL) were added followed by extraction with CH2Cl2 (2×5 mL). The organic extracts were dried over anhydrous Na2SO4 and removed in vacuo. Flash column chromatography (MeOH/CH2Cl2, 3:100) afforded 18 (52 mg, 95%), mp 96-98° C.; 1H NMR (400 MHz, CDCl3) δ 8.03-7.97 (m, 1H), 7.73-7.67 (m, 2H), 7.65-7.59 (m, 1H), 6.66 (br s, 1H), 6.58 (br s, 1H), 5.30 (br s, 1H), 5.21 (d, J=4.6 Hz, 1H), 3.63-3.52 (m, 3H), 3.40-3.32 (m, 6H), 2.46-2.35 (m, 5H), 2.01-0.98 (m, 29H), 1.42 (s, 9H), 0.95 (s, 3H), 0.91 (d, J=6.5 Hz, 3H), 0.87 (d, J=1.8 Hz, 3H), 0.86 (d, J=1.8 Hz, 3H), 0.66 (s, 3H); 13C NMR (75.5 MHz, CDCl3) δ 172.2, 171.8, 156.3, 148.1, 140.1, 134.0, 133.8, 131.9, 130.8, 124.3, 122.7, 79.3, 59.3, 56.8, 56.3, 50.1, 42.4, 41.8, 39.8, 39.7, 38.4, 37.8, 37.0, 36.7, 36.4 (×2), 36.3 (×2), 35.9, 35.8, 32.0 (×2), 31.9, 28.6 (×3), 28.4, 28.2, 27.7, 24.4, 24.0, 23.0, 22.7, 21.1, 19.6, 18.9, 12.0; IR (film) νmax 3378, 3284, 2935, 2867, 1688, 1643, 1548, 1366 cm−1; CI m/z 870.5407 (MH+, C47H76N5O8S requires 870.5415).

Workup

  1. extractionthe mixture was extracted with CH2Cl2 (2×5 mL)
  2. dry with materialthe combined organic extracts were dried over anhydrous Na2SO4, and solvent
  3. customwas removed in vacuo
  4. extractionfollowed by extraction with CH2Cl2 (2×5 mL)
  5. dry with materialThe organic extracts were dried over anhydrous Na2SO4
  6. customremoved in vacuo

Sources & evidence

ORD record
ord-82e271a277374255a8469d0f4fe53ac5
Source dataset
uspto-grants-2011_06
Patent number
US07956029B2

Reaction notes

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