4-Chlorophenyl Isocyanate → HCID 11619867, compound

HRID 1626189Notes

Reaction equation

HRID 1626189 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]=[C:9]=[O:10])=[CH:4][CH:3]=1.[NH2:11][C:12]1[CH:25]=[CH:24][C:15]([O:16][CH2:17][CH2:18][N:19]2[CH2:22][CH:21]([OH:23])[CH2:20]2)=[C:14]([C:26]2[N:27]([CH3:32])[N:28]=[CH:29][C:30]=2[Cl:31])[CH:13]=1>ClCCl.CN(C=O)C>[Cl:31][C:30]1[CH:29]=[N:28][N:27]([CH3:32])[C:26]=1[C:14]1[CH:13]=[C:12]([NH:11][C:9]([NH:8][C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)=[O:10])[CH:25]=[CH:24][C:15]=1[O:16][CH2:17][CH2:18][N:19]1[CH2:22][CH:21]([OH:23])[CH2:20]1

Participants

5

Reactant 2

HCID 76934-Chlorophenyl IsocyanateHCID 58964291HCID 58964291, compound

Product 1

HCID 11619867HCID 11619867, compoundYield 47.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

4-Chlorophenylisocyanate (19.0 mg, 0.124 mmol) was added to a solution of 1-{2-[4-amino-2-(4-chloro-2-methyl-2H-pyrazol-3-yl)-phenoxy]-ethyl}-azetidin-3-ol (40.0 mg, 0.124 mmol) in dichloromethane (2.0 mL) and DMF (0.1 mL), and the mixture stirred at room temperature overnight. The solution was concentrated and purified by RP-HPLC. The collected fractions were concentrated and 12% sodium hydroxide (aq) (0.2 mL) was added to give pH 9. The solution was extracted into ethyl acetate and the organic layer was dried over sodium sulfate, filtered, and evaporated to dryness to give a white solid (28 mg, 47%). LCMS m/z (%)=476 (M+H35Cl, 100), 478 (M+H37Cl, 67). 1H NMR (400 MHz, DMSO-d6) δ: 8.81 (bs, 1H), 8.71 (bs, 1H), 7.60 (s, 1H), 7.53-7.50 (m, 1H), 7.47 (d, J=2.08 Hz, 1H), 7.46 (d, J=2.10 Hz, 1H), 7.36 (d, J=2.71 Hz, 1H), 7.32 (d, J=2.11 Hz, 1H), 7.30 (d, J=2.04 Hz, 1H), 7.11 (d, J=9.06 Hz, 1H), 5.19 (d, J=8.00 Hz, 1H), 4.10-4.00 (m, 1H), 3.99-3.85 (m, 2H), 3.65 (s, 3H), 3.40-3.30 (m, 2H), 2.70-2.55 (m, 4H).

Workup

  1. concentrationThe solution was concentrated
  2. custompurified by RP-HPLC
  3. concentrationThe collected fractions were concentrated
  4. addition12% sodium hydroxide (aq) (0.2 mL) was added
  5. customto give pH 9
  6. extractionThe solution was extracted into ethyl acetate
  7. dry with materialthe organic layer was dried over sodium sulfate
  8. filtrationfiltered
  9. customevaporated to dryness

Sources & evidence

ORD record
ord-5a94b166e70f438a97e747f2505ebe08
Source dataset
uspto-grants-2014_07
Patent number
US08785441B2

Reaction notes

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