(S)-2-[4-(4-Amino-phenyl)-thiazol-2-ylcarbamoyl]-pyrrolidine-1-carboxylic acid benzyl ester → 2-[4-(4-Ureido-phenyl)-thiazol-2-yl carbamoyl]-pyrrolidine-1-carboxylic acid benzyl ester

HRID 737173Notes

Reaction equation

HRID 737173 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16](=[O:30])[NH:17][C:18]1[S:19][CH:20]=[C:21]([C:23]2[CH:28]=[CH:27][C:26]([NH2:29])=[CH:25][CH:24]=2)[N:22]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O1CCOCC1.[Si]([N:41]=[C:42]=[O:43])(C)(C)C>>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16](=[O:30])[NH:17][C:18]1[S:19][CH:20]=[C:21]([C:23]2[CH:24]=[CH:25][C:26]([NH:29][C:42]([NH2:41])=[O:43])=[CH:27][CH:28]=2)[N:22]=1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

3

Reactant 2

HCID 86616427(S)-2-[4-(4-Amino-phenyl)-thiazol-2-ylcarbamoyl]-pyrrolidine-1-carboxylic acid benzyl ester2×HCID 86616432dioxane TMS isocyanate

Product 1

HCID 591409232-[4-(4-Ureido-phenyl)-thiazol-2-yl carbamoyl]-pyrrolidine-1-carboxylic acid benzyl ester

Conditions

Temperature
70 °C

Procedure

2-[4-(4-Amino-phenyl)-thiazol-2-ylcarbamoyl]-pyrrolidine-1-carboxylic acid benzyl ester (Compound 5050, Example 50, 40 mg, 0.095 mmol) was dissolved in 4 ml of 1:1 dioxane/TMS isocyanate. Reaction mixture was heated at 70° C. for 7 hours. It was then evaporated to dryness. The crude was redissolved in 10 ml of DMF and purified on reverse phase HPLC. MS: 466.1 (M+H+); H1 NMR (DMSO-d6): δ(ppm) 12.39 (d, 1H), 7.72 (d, 2H), 7.42 (d, 3H), 7.35 (s, 2H), 7.10 (dd, 2H), 5.88 (br s, 2H), 5.02 (m, 2H), 4.50 (m, 1H), 2.25 (m, 2H), 1.90 (m, 4H).

Workup

  1. customReaction mixture
  2. customIt was then evaporated to dryness
  3. dissolutionThe crude was redissolved in 10 ml of DMF
  4. custompurified on reverse phase HPLC

Sources & evidence

ORD record
ord-9bf98091e533456692eb761d3b5c0e78
Source dataset
uspto-grants-2009_09
Patent number
US07595398B2

Reaction notes

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