Water → HCID 10676211, compound

HRID 343169Notes

Reaction equation

HRID 343169 reaction equation
[H-].[Na+].[O:3]=[C:4]1[N:10]([CH2:11][C:12]([N:14]([CH:24]([CH3:26])[CH3:25])[C:15]2[CH:20]=[CH:19][C:18]3[O:21][CH2:22][O:23][C:17]=3[CH:16]=2)=[O:13])[C:9]2[CH:27]=[CH:28][CH:29]=[CH:30][C:8]=2[N:7]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:6](=[O:37])[CH2:5]1.Br[CH2:39][C:40]1[C:48]2[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=2)[N:42]([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[N:41]=1.O>CN(C=O)C>[C:52]([O:51][C:49]([N:42]1[C:43]2[C:48](=[CH:47][CH:46]=[CH:45][CH:44]=2)[C:40]([CH2:39][CH:5]2[C:4](=[O:3])[N:10]([CH2:11][C:12]([N:14]([CH:24]([CH3:26])[CH3:25])[C:15]3[CH:20]=[CH:19][C:18]4[O:21][CH2:22][O:23][C:17]=4[CH:16]=3)=[O:13])[C:9]3[CH:27]=[CH:28][CH:29]=[CH:30][C:8]=3[N:7]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C:6]2=[O:37])=[N:41]1)=[O:50])([CH3:55])([CH3:54])[CH3:53]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 108049513-(Bromomethyl)-1H-indazole, N1-BOC protectedHCID 10814263HCID 10814263, compound

Product 1

HCID 10676211HCID 10676211, compoundYield 27.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

31 mg of Sodium Hydride (60% in oil) is added to a solution of 2-(-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydrobenzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(3,4-methylenedioxy-phenyl) acetamide (300 mg. 0.636 mmol) in DMF (10 mL ) and the resultant mixture stirred at RT for 0.5 h prior to the addition of 3-bromomethyl-1-tert-butoxycarbonyl-1H-indazole (197 mg, 0.636 mmol) to the reaction mixture. After 22 h, 10 mL of water is added and the resultant mixture extracted into ethyl acetate (3×10 mL). The combined organics were washed with water (3×10 mL), brine (10 mL), dried (MgSO4), and concentrated in vacuo to afford the crude product (460 mg) as a brown foam. Purification by silica gel flash column chromatography using 2% methanol in methylene chloride as eluent gave the desired product (123 mg) as a beige solid: 1H NMR (300 MHz, CDCl3) δ8.10 (d, 1H, J=8.6), 7.91 (d, 1H, J=8.0), 6.8-7.6 (m, 14H), 6.09 (s, 2H), 5.01 (m, 1H, J=6.9), 4.36 (m, 3H), 3.90 (dd, 1H, J=16.4, 8.8), 3.58 (m, 1H), 1.67 (s, 9H), 1.08 (m, 6H).

Workup

  1. extractionthe resultant mixture extracted into ethyl acetate (3×10 mL)
  2. washThe combined organics were washed with water (3×10 mL), brine (10 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customto afford the crude product (460 mg) as a brown foam
  6. customPurification by silica gel flash column chromatography

Sources & evidence

ORD record
ord-155b76c65ca14a8498f87d59c1126e23
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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