Water → HCID 10532638, compound

HRID 343174Notes

Reaction equation

HRID 343174 reaction equation
[H-].[Na+].[O:3]=[C:4]1[N:10]([CH2:11][C:12]([N:14]([CH:23]([CH3:25])[CH3:24])[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[O:21][CH3:22])=[O:13])[C:9]2[CH:26]=[CH:27][CH:28]=[CH:29][C:8]=2[N:7]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:6](=[O:36])[CH2:5]1.Br[CH2:38][C:39]1[C:47]2[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=2)[N:41]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[N:40]=1.O>CN(C=O)C>[C:51]([O:50][C:48]([N:41]1[C:42]2[C:47](=[CH:46][CH:45]=[CH:44][CH:43]=2)[C:39]([CH2:38][CH:5]2[C:4](=[O:3])[N:10]([CH2:11][C:12]([N:14]([CH:23]([CH3:25])[CH3:24])[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[O:21][CH3:22])=[O:13])[C:9]3[CH:26]=[CH:27][CH:28]=[CH:29][C:8]=3[N:7]([C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)[C:6]2=[O:36])=[N:40]1)=[O:49])([CH3:54])([CH3:53])[CH3:52]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 108049513-(Bromomethyl)-1H-indazole, N1-BOC protectedHCID 10813725HCID 10813725, compound

Product 1

HCID 10532638HCID 10532638, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

45 mg of Sodium Hydride (60% in oil, 1.12 mmol) 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-(2-methoxy-phenyl) acetamide, prepared as in Part D, (430 mg. 0.934 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 (291 mg, 0.934 mmol) to the reaction mixture. After stirring 22 h at RT, water (10 mL) 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 which is purified by silica gel flash column chromatography using 3% methanol in methylene chlorideas eluent to give the desired product (260 mg) as a beige solid, which exists as 3:2 mixture of rotamers (major rotamer recorded): 1H NMR (300 MHz, CDCl3) δ8.1 (t, 1H, J=8.0), 7.90 (m, 1H), 7.60-6.90 (m, 15H), 5.05 (m, 1H, J=6.9), 4.60-3.40 (m, 8H), 1.7 (s, 9H), 1.16 (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 which
  6. customis purified by silica gel flash column chromatography

Sources & evidence

ORD record
ord-1511dd506bc646efb173c3eab4ea116c
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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