Sodium Hydroxide → HCID 136348454, compound

HRID 1748812Notes

Reaction equation

HRID 1748812 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[S:14][CH2:13][CH:12]([C:15]([O:17]CC)=O)[NH:11][C:10]3[N:20]([CH3:29])[N:21]=[C:22]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=4)[C:9]2=3)=[C:4]([CH3:30])[CH:3]=1.[OH-].[Na+].[N:33]1(C(N2C=CN=C2)=O)C=CN=C1>O1CCOCC1.CN(C1C=CN=CC=1)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[S:14][CH2:13][CH:12]([C:15]([NH2:33])=[O:17])[NH:11][C:10]3[N:20]([CH3:29])[N:21]=[C:22]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=4)[C:9]2=3)=[C:4]([CH3:30])[CH:3]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 682631,1'-CarbonyldiimidazoleHCID 136348455HCID 136348455, compound

Product 1

HCID 136348454HCID 136348454, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of rac-(4R,7S)-ethyl 4-(4-bromo-2-methylphenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine-7-carboxylate (0.170 g, 0.174 mmol, Preparation #39) and 2 M NaOH (1 mL, 2.00 mmol) in 1,4-dioxane (2 mL) was stirred at rt for about 2 h. The reaction was partitioned between 1 M HCl (40 mL) and EtOAc (50 mL). The organic layer was washed with brine (50 mL), dried with Na2SO4, filtered and was concentrated in vacuo. The residue was suspended in THF (4 ml) and di(1H-imidazol-1-yl)methanone (0.085 g, 0.52 mmol) was added followed by DMAP (0.026 g, 0.21 mmol). The reaction was stirred at rt for about 1 h. The reaction was quenched with NH4OH (5.0 mL) and extracted with EtOAc (50 mL). The organic layer was washed with brine (50 mL), dried with Na2SO4, filtered and was concentrated in vacuo. The residue was recrystallized from DCM/Et2O to give rac-(4R,7S)-4-(4-bromo-2-methylphenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine-7-carboxamide (0.080 g, 0.087 mmol, 50%), as a white solid: LC-MS (Table 1, Method g) Rt=2.12 min, m/z 458/460 (M+H)+; 1H-NMR (DMSO-d6, Bruker 400 MHz) δ 8.43-8.40 (m, 1H), 7.81-7.77 (m, 1H), 7.73-7.65 (m, 1H), 7.34 (d, J=1.8 Hz, 1H), 7.23-7.19 (m, 1H), 7.17-7.12 (m, 1H), 7.11-7.08 (m, 2H), 6.99 (s, 1H), 6.61 (s, 1H), 5.82 (d, J=5.0 Hz, 1H), 4.11-4.07 (m, 1H), 3.77 (s, 3H), 3.20 (dd, J=15.2, 5.5 Hz, 1H), 2.83 (dd, J=15.3, 2.8 Hz, 1H), 2.48 (s, 3H).

Workup

  1. customThe reaction was partitioned between 1 M HCl (40 mL) and EtOAc (50 mL)
  2. washThe organic layer was washed with brine (50 mL)
  3. dry with materialdried with Na2SO4
  4. filtrationfiltered
  5. concentrationwas concentrated in vacuo
  6. stirringThe reaction was stirred at rt for about 1 h
  7. customThe reaction was quenched with NH4OH (5.0 mL)
  8. extractionextracted with EtOAc (50 mL)
  9. washThe organic layer was washed with brine (50 mL)
  10. dry with materialdried with Na2SO4
  11. filtrationfiltered
  12. concentrationwas concentrated in vacuo
  13. customThe residue was recrystallized from DCM/Et2O

Sources & evidence

ORD record
ord-30adea6be0b8453b84afbec6aeacbf03
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

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