Triphenylphosphine → HCID 11627746, compound

HRID 1626221Notes

Reaction equation

HRID 1626221 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][N:5]([CH3:25])[C:6]=1[C:7]1[CH:8]=[C:9]([NH:14][C:15]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)=[O:16])[CH:10]=[CH:11][C:12]=1[OH:13].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[CH2:46][CH2:47][N:48]1[CH2:52][CH2:51][CH2:50][CH2:49]1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[Br:1][C:2]1[CH:3]=[N:4][N:5]([CH3:25])[C:6]=1[C:7]1[CH:8]=[C:9]([NH:14][C:15]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)=[O:16])[CH:10]=[CH:11][C:12]=1[O:13][CH2:46][CH2:47][N:48]1[CH2:52][CH2:51][CH2:50][CH2:49]1

Participants

6

Reactant 4

HCID 11776Triphenylphosphine2×HCID 75555Diisopropyl diazene-1,2-dicarboxylate2×HCID 762881-Pyrrolidineethanol2×HCID 1355074951-(3-(4-bromo-1-methyl-1H-pyrazol-5-yl)-4-hydroxyphenyl)-3-(4-chlorophenyl)urea

Product 1

HCID 11627746HCID 11627746, compoundYield 57.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-(3-(4-bromo-1-methyl-1H-pyrazol-5-yl)-4-hydroxyphenyl)-3-(4-chlorophenyl)urea (44.3 mg, 0.105 mmol) in THF (5 mL), was added triphenyl phosphine (66.2 mg, 0.252 mmol) and 1-(2-hydroxyethyl)pyrrolidine (28.0 mg, 0.243 mmol) followed by dropwise addition of diisopropyl azodicarboxylate (DIAD) (50 μL, 0.258 mmol). After 1 hour, an LC/MS showed only partial conversion so extra triphenyl phosphine (36.9 mg, 0.141 mmol) and 1-(2-hydroxyethyl)pyrrolidine (17 μL, 0.145 mmol) was added followed by dropwise addition of diisopropyl azodicarboxylate (DIAD) (27 μL, 0.139 mmol). The reaction mixture was stirred at room temperature for 1 more hour and then concentrated. The resulting material was purified by HPLC. The product was dried in vacuo to afford the title compound as a light brown solid (31.3 mg, 57%). LCMS m/z (%)=520 (M+H81Br, 100), 518 (M+H79Br, 73), 1H NMR (400 MHz, DMSO-d6) δ 8.81 (bs, 1H), 8.71 (bs, 1H), 7.60 (s, 1H), 7.53 (dd, J=8.98, 2.72 Hz, 1H), 7.47 (d, J=8.95 Hz, 2H), 7.35 (d, J=2.71 Hz, 1H), 7.31 (d, J=8.90 Hz, 2H), 7.15 (d, J=9.05 Hz, 1H), 4.15-4.07 (m, 1H), 4.06-3.98 (m, 1H), 3.66 (s, 3H), 2.80-2.69 (m, 1H), 2.69-2.58 (m, 1H), 2.42-2.31 (m, 4H), 1.66-1.55 (m, 4H).

Workup

  1. additionwas added
  2. concentrationconcentrated
  3. customThe resulting material was purified by HPLC
  4. customThe product was dried in vacuo

Sources & evidence

ORD record
ord-ba3b61df30a74a60b7e09bd260aafdf3
Source dataset
uspto-grants-2014_07
Patent number
US08785441B2

Reaction notes

Loading…