4-Chlorophenyl Isocyanate → HCID 11619867, compound

HRID 1362961Notes

Reaction equation

HRID 1362961 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+H 35Cl, 100), 478 (M+H 37Cl, 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, 11H), 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, 311), 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-e0db95dc158e47ab8cc7ee43a0aad2cc
Source dataset
uspto-grants-2011_02
Patent number
US07884101B2

Reaction notes

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