Ammonium Chloride → HCID 86753594, compound

HRID 343166Notes

Reaction equation

HRID 343166 reaction equation
[CH3:1][CH:2]1[C:8](=[O:9])[N:7]([CH2:10][C:11]([N:13]([CH:22]([CH3:24])[CH3:23])[C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)=[O:12])[C:6]2[CH:25]=[CH:26][CH:27]=[CH:28][C:5]=2[N:4]([C:29]2[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=2)[C:3]1=[O:35].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Br[CH2:47][C:48]1[C:56]2[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=2)[N:50]([C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[N:49]=1.[NH4+].[Cl-]>CN(C=O)C.C1COCC1>[CH3:1][C:2]1([CH2:47][C:48]2[C:56]3[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=3)[N:50]([C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[N:49]=2)[C:8](=[O:9])[N:7]([CH2:10][C:11]([N:13]([CH:22]([CH3:23])[CH3:24])[C:14]2[CH:15]=[CH:16][C:17]([O:20][CH3:21])=[CH:18][CH:19]=2)=[O:12])[C:6]2[CH:25]=[CH:26][CH:27]=[CH:28][C:5]=2[N:4]([C:29]2[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=2)[C:3]1=[O:35]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 108049513-(Bromomethyl)-1H-indazole, N1-BOC protectedHCID 67696539HCID 67696539, compound

Product 1

HCID 86753594HCID 86753594, compoundYield 69.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of 2.33 g (4.93 mmol) of 2-(3-Methyl-2,4-dioxo-5-pyridin-3-yl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl)-acetamide, prepared as in Part A, in 50 mL of DMF at 0° C. is added 5.42 mL (5.42 mmol) of a 1.0M solution of NaN(TMS)2 in THF. The resulting solution is stirred 10 min, then a solution of 1.69 g (5.42 mmol) of 3-bromomethyl-1-tert-butoxycarbonyl-1H-indazole in 10 mL of DMF is added. The resulting solution is stirred at RT for 2 h then poured into 100 mL NH4Cl. The reaction mixture is concentrated to remove the DMF, diluted with 300 mL of H2O and extracted with EtOAc (3×200 mL). The organics were dried (MgSO4), and the solvents removed in vacuo. Purification by silica gel flash chromatography using hexane/EtOAc 3/1 as eluent afforded 2.41 g of the title compound as a light yellow foam: 1H NMR (CDCl3, 400 MHz) δ8.53 (m, 2H), 8.06 (m, 2H), 7.50-6.96 (m, 12H), 5.03 (m,1H), 4.58 (d, 1H), 4.06 (d, 1H), 3.85 (s, 3H), 3.02 (dd, AB quartet, 2H, J=16.8), 1.72 (s, 9H), 1.55 (s, 3H), 1.14 (d, 6H, J=6.8); low resolution MS (FAB)m/e 703 (MH+), 603, 438; Anal. (C40H42N6O6) Calcd. C, 68.36; H, 6.02; N, 11.96 Found C, 67.11; H, 6.15; N, 11.48.

Workup

  1. stirringThe resulting solution is stirred at RT for 2 h
  2. concentrationThe reaction mixture is concentrated
  3. customto remove the DMF
  4. additiondiluted with 300 mL of H2O
  5. extractionextracted with EtOAc (3×200 mL)
  6. dry with materialThe organics were dried (MgSO4)
  7. customthe solvents removed in vacuo
  8. customPurification by silica gel flash chromatography

Sources & evidence

ORD record
ord-88bda3fa418e42b6b520c8bf8408eee1
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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