Potassium Carbonate → HCID 67198449, compound

HRID 336126Notes

Reaction equation

HRID 336126 reaction equation
[NH2:1][C@H:2]1[CH2:26][CH2:25][C@@:24]2([CH3:27])[C:4](=[CH:5][CH2:6][C@@H:7]3[C@@H:23]2[CH2:22][CH2:21][C@@:20]2([CH3:28])[C@H:8]3[CH2:9][CH2:10][C@@H:11]2[C@H:12]([CH3:19])[CH2:13][CH2:14][CH2:15][CH:16]([CH3:18])[CH3:17])[CH2:3]1.Br[CH2:30][CH2:31][CH2:32][N:33]1[C:37](=[O:38])[C:36]2=[CH:39][CH:40]=[CH:41][CH:42]=[C:35]2[C:34]1=[O:43].C([O-])([O-])=O.[K+].[K+].[CH3:50][C:51]([O:54][C:55](OC(OC(C)(C)C)=O)=[O:56])([CH3:53])[CH3:52].CCN(C(C)C)C(C)C>CN(C=O)C>[C:51]([O:54][C:55](=[O:56])[N:1]([C@H:2]1[CH2:26][CH2:25][C@@:24]2([CH3:27])[C:4](=[CH:5][CH2:6][C@@H:7]3[C@@H:23]2[CH2:22][CH2:21][C@@:20]2([CH3:28])[C@H:8]3[CH2:9][CH2:10][C@@H:11]2[C@H:12]([CH3:19])[CH2:13][CH2:14][CH2:15][CH:16]([CH3:18])[CH3:17])[CH2:3]1)[CH2:30][CH2:31][CH2:32][N:33]1[C:37](=[O:38])[C:36]2[C:35](=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:34]1=[O:43])([CH3:53])([CH3:52])[CH3:50]

Participants

7

Reactant 5

HCID 11430Potassium CarbonateHCID 21611N-3-BromopropylphthalimideHCID 81531DiisopropylethylamineHCID 90495Di-tert-butyl dicarbonateHCID 91512Cholesterylamine2×

Product 1

HCID 67198449HCID 67198449, compoundYield 69.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To DMF (10 mL) were added 3β-amino-5-cholestene (Compound 8, 386 mg, 1.0 mmol), N-(3-bromopropyl)phthalimide (295 mg, 1.1 mmol), and K2CO3 (276 mg, 2.0 mmol). The solution was heated to 60° C. and stirred for 24 h. The reaction was cooled to 22° C., and DMF was removed in vacuo. To the resulting residue was added CH2Cl2 (10 mL). The insoluble material was removed by filtration and washed with additional CH2Cl2 (2×5 mL). To the combined filtrate and wash solutions containing the crude secondary amine product was added (Boc)2O (327 mg, 1.5 mmol) and DIEA (0.5 mL, 3.0 mmol). The reaction was stirred for 4 h at 22° C. and concentrated in vacuo. Flash column chromatography (hexanes/ethyl acetate, 8:1) afforded Compound 9 (465 mg, 69%) as a white foam, mp 59-61° C.; 1H NMR (400 MHz, CDCl3) δ 7.83 (m, 2H), 7.69, (m, 2H), 5.30 (d, 1H), 3.68 (t, 2H), 3.13 (br, 3H), 2.01-0.83 (m, 51H), 0.65 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 168.2 (×2), 155.2, 141.3, 133.8 (×2), 132.0 (×2), 123.2 (×2), 79.3, 56.6, 56.1 (×2), 50.1, 42.6 (×2), 39.8, 39.4 (×2), 38.3, 36.8, 36.5, 36.1, 35.9, 35.7, 31.2 (×2), 28.4 (Boc, Me3), 28.2, 27.9, 26.7, 24.2, 23.8 (×2), 22.8, 22.5, 20.9, 19.3, 18.7, 11.8; IR (film) ν max 2935, 2867, 1772, 1715, 1689, 1467, 1395, 1365, 1238, 1172, 1146, 1031, 888, 756, 720 cm−1; HRMS (CI+) m/z 673.4946 (M+H+, C43H65N2O4, requires 673.4944).

Workup

  1. temperatureThe reaction was cooled to 22° C.
  2. customDMF was removed in vacuo
  3. additionTo the resulting residue was added CH2Cl2 (10 mL)
  4. customThe insoluble material was removed by filtration
  5. washwashed with additional CH2Cl2 (2×5 mL)
  6. washTo the combined filtrate and wash solutions
  7. additioncontaining the crude secondary amine product
  8. stirringThe reaction was stirred for 4 h at 22° C.
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-22f9f69fc474414eacb9838d6a4e9cca
Source dataset
uspto-grants-2014_11
Patent number
US08889631B2

Reaction notes

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