Diisopropylcarbodiimide → HCID 178454228, compound

HRID 2075771Notes

Reaction equation

HRID 2075771 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:30])=[C:6]([C:8]2[C:12]([C:13]#[C:14][C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22]([C@@H:24]4[CH2:29][CH2:28][CH2:27][CH2:26][NH:25]4)=[O:23])=[CH:17][CH:16]=3)=[CH:11][NH:10][N:9]=2)[CH:7]=1.[NH:31]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[C@@H:32]([C:39](O)=[O:40])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.CC(C)N=C=NC(C)C>C1COCC1>[C:45]([O:44][C:42](=[O:43])[NH:31][C@H:32]([C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)[C:39]([N:25]1[CH2:26][CH2:27][CH2:28][CH2:29][C@H:24]1[C:22](=[O:23])[NH:21][C:18]1[CH:17]=[CH:16][C:15]([C:14]#[C:13][C:12]2[C:8]([C:6]3[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=3[OH:30])=[N:9][NH:10][CH:11]=2)=[CH:20][CH:19]=1)=[O:40])([CH3:48])([CH3:46])[CH3:47]

Participants

5

Reactant 3

HCID 12734DiisopropylcarbodiimideHCID 2755953(2R)-2-{[(tert-butoxy)carbonyl]amino}-2-phenylacetic acidHCID 178522030HCID 178522030, compound

Product 1

HCID 178454228HCID 178454228, compoundYield 37.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of compound 26A (468 mg, 1.11 mmol) and BOC-D-Phg-OH (11A, 280 mg, 1.11 mmol) was added anhydrous THF (10 mL) and the resultant mixture was stirred at rt for 5 min. DIPC (0.258 mL, 1.67 mmol) was added slowly at rt. The reaction mixture was stirred at rt overnight. Solvent was removed. The residua were dissolved in a small amount of ethyl acetate. Solid was removed by filtration. The filtrate was purified by silica column chromatography eluting with hexanes-ethyl acetate (v/v 3/1, 2/1, 1/1) to provide the title compound (27A, 275 mg) as an off-color foam-like powder in 37.8% yield. 1H NMR (CDCl3, 500 MHz) δ 10.74 (br s, 2H), 8.75 (s, 1H), 8.52 (s, 1H), 7.82 (d, 2H, J=8.0 Hz), 7.79 (s, 1H), 7.58 (d, 2H, J=8.5 Hz), 7.43 (m, 5H), 7.21 (dd, 1H, J=8.0, 2.0 Hz), 6.98 (d, 1H, J=9.0 Hz), 5.61 (d, 1H, J=6.5 Hz), 5.56 (s, 2H), 3.90 (d, 1H, J=12.5 Hz), 3.20 (t, 1H, J=12.0 Hz), 2.51 (m, 1H), 1.62 (m, 2H), 1.55-1.30 (m, 11H), 0.91 (m, 1H). LCMS (ESI) m/z 720.27 (MNa+), 676.17 (MNa+), 654.22 (MH+), 554.11, 345.17, 289.12 (100). HPLC: tR=5.55 min.

Workup

  1. customSolvent was removed
  2. dissolutionThe residua were dissolved in a small amount of ethyl acetate
  3. customSolid was removed by filtration
  4. customThe filtrate was purified by silica column chromatography
  5. washeluting with hexanes-ethyl acetate (v/v 3/1, 2/1, 1/1)

Sources & evidence

ORD record
ord-d13c0676df2547af882f2870e1aaa0d3
Source dataset
uspto-grants-2011_04
Patent number
US07923004B2

Reaction notes

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