Dimethylformamide → HCID 11444269, compound

HRID 1825368Notes

Reaction equation

HRID 1825368 reaction equation
CN(C=O)C.[CH2:6]([NH2:8])[CH3:7].[CH:9]1([CH2:15][CH2:16][CH2:17][CH2:18][NH:19][C:20]([C:22]2[N:23]=[C:24]([C@@H:27]3[CH:32]4[O:33][C@@H:29]([CH2:30][CH2:31]4)[C@@H:28]3[CH2:34][C:35]3[CH:40]=[C:39]([F:41])[CH:38]=[CH:37][C:36]=3[CH2:42][CH2:43][C:44]([OH:46])=O)[O:25][CH:26]=2)=[O:21])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1.Cl.CN(C)CCCN=C=NCC>CN(C1C=CN=CC=1)C.C(OCC)(=O)C>[CH:9]1([CH2:15][CH2:16][CH2:17][CH2:18][NH:19][C:20]([C:22]2[N:23]=[C:24]([CH:27]3[CH:28]([CH2:34][C:35]4[CH:40]=[C:39]([F:41])[CH:38]=[CH:37][C:36]=4[CH2:42][CH2:43][C:44](=[O:46])[NH:8][CH2:6][CH3:7])[CH:29]4[O:33][CH:32]3[CH2:31][CH2:30]4)[O:25][CH:26]=2)=[O:21])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 6341EthylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 23573773HCID 23573773, compound

Product 1

HCID 11444269HCID 11444269, compoundYield 20.8%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8857Ethyl AcetateSolvent

Procedure

DMF (0.22 mL) and ethyl amine (77 μL, 0.15 mmol) were added to 3-(2-{(1S,2R,3S)-3-[4-(4-Cyclohexyl-butylcarbamoyl)-oxazol-2yl]-7-oxa-bicyclo[2.2.1]hept-2-ylmethyl}-4-fluoro-phenyl)-propionic acid (1) (28 mg, 0.053 mmol), EDCI [1-(3-dimehylaminopropyl)-3-ethylcarbodiimide hydrochloride] (17 mg, 0.089 mmol) and DMAP (8 mg, 0.065 mmol). The solution was stirred for 23 h and then was diluted with 15 mL ethyl acetate and washed with HCl (1 M, 3×15 mL). The ethyl acetate solution was then dried (Na2SO4), filtered and evaporated. Flash chromatography on silica gel (ethyl acetate) gave a mixture of the starting acid and the product amide. Purification by preparative thin layer chromatography (4% methanol/dichloromethane) gave the title amide (6 mg, 0.011 mmol, 20%). 1H NMR (300 MHz, ppm) δ 8.06 (s, 1 H) 7.1–7.0 (m, 2 H) 6.8–6.7 (m, 2 H) 5.43 (br s, 1 H) 4.97 (d, J=4.4 Hz, 1 H) 4.82 (d, J=4.4 Hz, 1 H) 3.4–3.3 (m, 3 H) 3.3–3.2 (m, 2 H) 2.9–2.8 (m, 2 H) 2.6–2.5 (m, 1 H) 2.3–2.1 (m, 4 H) 1.8–0.8 (m, 24 H).

Workup

  1. washwashed with HCl (1 M, 3×15 mL)
  2. dry with materialThe ethyl acetate solution was then dried (Na2SO4)
  3. filtrationfiltered
  4. customevaporated
  5. customFlash chromatography on silica gel (ethyl acetate) gave
  6. additiona mixture of the starting acid
  7. customPurification by preparative thin layer chromatography (4% methanol/dichloromethane)

Sources & evidence

ORD record
ord-efdfb2bd7c40444c979253a08008c9cc
Source dataset
uspto-grants-2006_05
Patent number
US07045634B2

Reaction notes

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