Trifluoroacetic acid → 2-[7,8-Difluoro-3-(1H-indazol-3-ylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl)-acetamide

HRID 343232Notes

Reaction equation

HRID 343232 reaction equation
FC(F)(F)C(O)=O.[F:8][C:9]1[C:59]([F:60])=[CH:58][C:12]2[N:13]([CH2:43][C:44]([N:46]([CH:55]([CH3:57])[CH3:56])[C:47]3[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][CH:48]=3)=[O:45])[C:14](=[O:42])[CH:15]([CH2:25][C:26]3[C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[N:28](C(OC(C)(C)C)=O)[N:27]=3)[C:16](=[O:24])[N:17]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:11]=2[CH:10]=1>>[F:8][C:9]1[C:59]([F:60])=[CH:58][C:12]2[N:13]([CH2:43][C:44]([N:46]([CH:55]([CH3:57])[CH3:56])[C:47]3[CH:48]=[CH:49][C:50]([O:53][CH3:54])=[CH:51][CH:52]=3)=[O:45])[C:14](=[O:42])[CH:15]([CH2:25][C:26]3[C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[NH:28][N:27]=3)[C:16](=[O:24])[N:17]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:11]=2[CH:10]=1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 867535922-[7,8-difluoro-3-(1-tertbutoxycarbonyl-indazol-3-ylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl)-acetamide

Product 1

HCID 1784923812-[7,8-Difluoro-3-(1H-indazol-3-ylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl)-acetamideYield 99.8%

Procedure

To a solution of 5.0 mL trifluoroacetic acid under nitrogen is added 0.500 g of 2-[7,8-difluoro-3-(1-tertbutoxycarbonyl-indazol-3-ylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl)-acetamide, prepared as in Intermediate 67, (0.697 mmol). After stirring for 1.5 hrs., the trifluoroacetic acid is removed in vacuo and the residue is partitioned between methylene chloride and aqueous sodium hydroxide (1N) and transferred to a separatory funnel. The layers were separated and the organic layer is back-extracted with methylene chloride. The organic layers were combined, dried over anhydrous sodium sulfate, filtered, evaporated in vacuo to a residue and then triturated with hexane. Hexane is removed in vacuo and the remaining solid is dried under high vacuum to provide 430 mg of the title compound as an off-white solid: 1H NMR (300 MHz, CDCl3) δ7.93 (d, 1H, J=8.2), 7.51 (m, 2H), 7.41 (m, 2H), 7.29 (m, 7H), 7.15 (m, 1H), 7.00 (m, 2H), 6.82 (m, 1H), 5.01 (m, 1H), 4.36 (m, 1H), 4.32 (d, 1H, J=17.1), 4.19 (d, 1H, J=16.7), 3.88 (s, 3H), 3.87 (m, 1H), 3.74 (dd, 1H, J=6.0, 16.1), 1.10 (d, 6H, J=6.8); low resolution MS (FAB)m/e 624 (MH+).

Workup

  1. custom, the trifluoroacetic acid is removed in vacuo
  2. customthe residue is partitioned between methylene chloride and aqueous sodium hydroxide (1N)
  3. customtransferred to a separatory funnel
  4. customThe layers were separated
  5. extractionthe organic layer is back-extracted with methylene chloride
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. customevaporated in vacuo to a residue
  9. customtriturated with hexane
  10. customHexane is removed in vacuo
  11. customthe remaining solid is dried under high vacuum

Sources & evidence

ORD record
ord-2a9457f03eb24db88ba0253495a6d8c6
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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