Methanol → HCID 11952998, compound

HRID 1241464Notes

Reaction equation

HRID 1241464 reaction equation
[C:1]([O:5][C:6](=[O:41])[CH2:7][CH2:8][CH2:9][CH2:10][N:11]1[C:17]2[CH:18]=[CH:19][C:20](I)=[CH:21][C:16]=2[C:15](=[O:23])[N:14]([C@@H:24]([C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=2)[CH3:25])[C@@H:13]([C:33]2[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][CH:34]=2)[C:12]1=[O:40])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:49][OH:50].CN([CH:54]=[O:55])C>>[C:1]([O:5][C:6](=[O:41])[CH2:7][CH2:8][CH2:9][CH2:10][N:11]1[C:17]2[CH:18]=[CH:19][C:20]([C:49]([O:55][CH3:54])=[O:50])=[CH:21][C:16]=2[C:15](=[O:23])[N:14]([C@@H:24]([C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=2)[CH3:25])[C@@H:13]([C:33]2[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][CH:34]=2)[C:12]1=[O:40])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 4

HCID 887MethanolHCID 6228DimethylformamideHCID 8471TriethylamineHCID 69338612HCID 69338612, compound

Product 1

HCID 11952998HCID 11952998, compoundYield 83%

Procedure

A solution of 5-[(3S)-3-(4-chlorophenyl)-4-[(R)-1-(4-chlorophenyl)ethyl]-7-iodo-2,5-dioxo-3,4-dihydro-1H-1,4-benzodiazepin-1-yl]valeric acid tert-butyl ester (300 mg, 0.42 mmol), dichloro bis-(triphenylphosphine)Pd(II) (21 mg, 0.030 mmol), and triethylamine (200 μL, 1.43 mmol), in DMF (4 mL) and methanol (1.5 mL) was stirred under a carbon monoxide atmosphere at 80° C. for 24 h. After the solution was cooled to room temperature, the solvent was evaporated under reduced pressure. The crude reaction product was purified by column chromatography on silica gel (EtOAc/hexanes, 1:2) to give the title compound (226 mg, 83%): 1H NMR (400 MHz, CDCl3) δ 1.45 (s, 9H, 3 CH3), 1.58–1.62 (m, 2H, CH2), 1.75 (d, J=5.4 Hz, 3H, CH3), 2.24 (t, J=10.5 Hz, 2H, CH2), 3.62–3.90 (m, 3H, 3 CH), 3.91 (s, 3H, CH3), 4.23–4.31 (m, 1H, CH), 5.34 (s, 1H, CH), 6.45 (q, J=5.4 Hz, 1H, CH), 6.50 (d, J=6.3 Hz, 2H, ArH), 6.84 (d, J=6.3 Hz, 2H, ArH), 6.94 (d, J=6.6 Hz, 1H, ArH), 7.32 (d, J=6.6 Hz, 2H, ArH), 7.50 (d, J=6.3 Hz, 2H, ArH), 7.84 (dd, J=6.3 Hz, J=1.5 Hz, 1H, ArH), 8.33 (d, J=1.5 Hz, 1H, ArH).

Workup

  1. customthe solvent was evaporated under reduced pressure
  2. customThe crude reaction product
  3. customwas purified by column chromatography on silica gel (EtOAc/hexanes, 1:2)

Sources & evidence

ORD record
ord-b1f7b58376934efe9dc0b9fa26539abe
Source dataset
uspto-grants-2006_10
Patent number
US07115598B2

Reaction notes

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