4-Methylmorpholine → HCID 11764213, compound

HRID 1174344Notes

Reaction equation

HRID 1174344 reaction equation
[NH2:1][C@@H:2]([CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[C@@H:3]([OH:38])[CH2:4][C@@H:5]([NH:13][C:14](=[O:37])[C@@H:15]([N:20]1[CH2:24][CH2:23][N:22]([CH2:25][C:26]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[N:29]=[CH:28][CH:27]=2)[C:21]1=[O:36])[C@@H:16]([CH3:19])[CH2:17][CH3:18])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH3:46][O:47][C:48]([NH:50][C@@H:51]([C:55]([CH3:58])([CH3:57])[CH3:56])[C:52](O)=[O:53])=[O:49].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>CN(C=O)C>[CH2:39]([C@H:2]([NH:1][C:52]([C@@H:51]([NH:50][C:48](=[O:49])[O:47][CH3:46])[C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[C@@H:3]([OH:38])[CH2:4][C@@H:5]([NH:13][C:14](=[O:37])[C@@H:15]([N:20]1[CH2:24][CH2:23][N:22]([CH2:25][C:26]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[N:29]=[CH:28][CH:27]=2)[C:21]1=[O:36])[CH:16]([CH3:19])[CH2:17][CH3:18])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 11263950N-(Methoxycarbonyl)-L-tert-leucineHCID 67407508HCID 67407508, compound

Product 1

HCID 11764213HCID 11764213, compoundYield 17%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

A solution containing the product from Example 134B (0.147 mmol) in DMF (2 mL) was treated with the product from Example 1F (0.035 g, 0.185 mmol), EDAC (0.045 g, 0.235 mmol), HOBT (0.030g, 0.222 mmol), and NMM (0.050 mL, 0.455 mmol) at 0° C., stirred at 25° C. for 16 hours, and partitioned between ethyl acetate and water. The organic phase was washed with 10% citric acid, dilute sodium bicarbonate, and brine, dried over MgSO4, filtered and concentrated. The residue was purified by reversed phase chromatography on a C18 column, eluting with 5-100% acetonitrile in water (0.1% TFA) to give the title compound (0.019 g, 17% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.68 (d, J=6.6 Hz, 3 H), 0.93 (m, 12 H), 0.88-0.97 (m, 1 H), 1.22-1.33 (m, 1H), 1.47-1.56 (m, 2H), 1.72-1.84 (m, 1H), 2.38-2.45 (m, 1H), 2.62-2.73 (m, 3H), 2.79-2.86 (m, 1H), 2.98-3.10 (m, 3H), 3.55-3.63 (m, 4H), 3.89-3.94 (m, 2H), 4.07-4.21 (m, 2H), 4.80 (s, 2H), 6.79 (d, J=9.56 Hz, 1 H), 6.93-7.20 (m, 10 H), 7.41 (d, J=4.41 Hz, 1 H), 7.48-7.53 (m, 1H), 7.57-7.62 (m, 1H), 7.75-7.80 (m, 1H), 7.87 (d, J=9.19 Hz, 1 H), 8.06 (d, J=8.45 Hz, 1 H), 8.30 (d, J=8.08 Hz, 1 H), 8.88 (d, J=4.41 Hz, 1 H).

Workup

  1. custompartitioned between ethyl acetate and water
  2. washThe organic phase was washed with 10% citric acid, dilute sodium bicarbonate, and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by reversed phase chromatography on a C18 column
  7. washeluting with 5-100% acetonitrile in water (0.1% TFA)

Sources & evidence

ORD record
ord-67e69f23e6a1417c875a5ef66d5fcf92
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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