Triethylamine → HCID 57968845, compound

HRID 1483764Notes

Reaction equation

HRID 1483764 reaction equation
[NH2:1][CH2:2][C:3]1[CH:19]=[CH:18][C:6]([O:7][C:8]2[CH:17]=[CH:16][C:11]3[B:12]([OH:15])[O:13][CH2:14][C:10]=3[CH:9]=2)=[CH:5][CH:4]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(CC)CC.[C:48]([O:52][C:53]([NH:55][CH:56]([CH3:60])[C:57](O)=[O:58])=[O:54])([CH3:51])([CH3:50])[CH3:49]>C(Cl)Cl.O>[C:48]([O:52][C:53](=[O:54])[NH:55][CH:56]([C:57](=[O:58])[NH:1][CH2:2][C:3]1[CH:19]=[CH:18][C:6]([O:7][C:8]2[CH:17]=[CH:16][C:11]3[B:12]([OH:15])[O:13][CH2:14][C:10]=3[CH:9]=2)=[CH:5][CH:4]=1)[CH3:60])([CH3:49])([CH3:50])[CH3:51]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 2684712-N-Boc-aminopropionic acidHCID 57968923Crisaborole intermediate

Product 1

HCID 57968845HCID 57968845, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a 40 mL scintillation vial containing 5-(4-aminomethyl-phenoxy)-3H-benzo[c][1,2]oxaborol-1-ol (350 mg, 1.37 mmol, 1.0 eq.), EDCI (314.4 mg, 1.64 mmol, 1.2 eq.), HOBt (221.6 mg, 1.64 mmol, 1.2 eq.) and Et3N (0.46 mL mg, 3.29 mmol, 2.4 eq.) in DCM (15.0 mL) was added 2-tert-Butoxycarbonylamino-propionic acid (311.1 mg, 1.64 mmol, 1.2 eq.) drop wise. The mixture was stirred at room temperature overnight. The mixture was treated with H2O (10 mL) and the layers were separated. The aqueous was extracted with DCM (2×10 mL), combined organic phase was washed with brine (10 mL), dried over MgSO4, filtered and the filtrate was concentrated under reduced pressure. The residue was applied to silica chromatography eluting with MeOH/DCM (0:100 to 10:90) to give {1-[4-(1-hydroxy-1,3-dihydro-benzo[c][1,2]oxaborol-5-yloxy)-benzylcarbamoyl]-ethyl}-carbamic acid tert-butyl ester as a white solid. LCMS (m/z) 449 (M+23); 1H NMR (DMSO-d6) δ: 9.08 (s, 1H), 8.26 (t, J=5.7 Hz, 1H), 7.68 (d, J=8.0 Hz, 1H), 7.22-7.31 (m, J=8.4 Hz, 2H), 6.96-7.01 (m, J=8.5 Hz, 2H), 6.88-6.95 (m, 3H), 4.89 (s, 2H), 4.21-4.30 (m, 2H), 3.88-4.02 (m, 1H), 1.35 (s, 9H), 1.18 (d, J=7.1 Hz, 3H).

Workup

  1. customthe layers were separated
  2. extractionThe aqueous was extracted with DCM (2×10 mL)
  3. washwas washed with brine (10 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. washeluting with MeOH/DCM (0:100 to 10:90)

Sources & evidence

ORD record
ord-2d09a0b024584c2bbf0deade501dcd2b
Source dataset
uspto-grants-2016_08
Patent number
US09416146B2

Reaction notes

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