Ammonia → HCID 136348436, compound

HRID 1748768Notes

Reaction equation

HRID 1748768 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[CH:12]1[S:18][CH2:17][CH2:16][NH:15][C:14]2[N:19]([CH3:28])[N:20]=[C:21]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[C:13]1=2)[C:5]([O:7]C)=O.[C-]#[N:30].[K+].N>CO>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[CH:12]1[S:18][CH2:17][CH2:16][NH:15][C:14]2[N:19]([CH3:28])[N:20]=[C:21]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[C:13]1=2)[C:5]([NH2:30])=[O:7]

Participants

5

Reactant 3

HCID 222AmmoniaHCID 9032Potassium CyanideHCID 136348416HCID 136348416, compound

Product 1

HCID 136348436HCID 136348436, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of methyl 3-chloro-4-[1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-4-yl]benzoate (0.14 g, 0.32 mmol, Example #E.1), methanol (15 mL), potassium cyanide (0.02 g, 0.3 mmol), and ammonia (10 mL, 7 M in MeOH, 70 mmol) was heated, in a sealed flask, for about 18 h at about 110° C. After cooling to rt the mixture was concentrated in vacuo. The residue was dissolved in DCM (100 mL) and washed with water (2×40 mL). The organic layer was dried (MgSO4), filtered, and concentrated in vacuo. The residue was purified by prep-HPLC (Table 2, Method a,) to give 3-chloro-4-[1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-4-yl]benzamide as an off white solid (0.018 g, 0.05 mmol, 16%): LC-MS (Table 1, Method b) Rt=4.5 min; m/z 400 (M+H)+; 1H-NMR (CDCl3, Bruker 400 MHz) δ 2.63-2.72 (1H, m) 2.75-2.86 (1H, m) 3.18-3.28 (1H, m) 3.75-3.75 (1H, m) 3.83 (3H, s) 4.78 (1H, br.d, J=5.5 Hz) 6.23 (1H, br. s) 6.91 (1H, s) 7.08 (1H, ddd, J=8.0, 5.0, 1.0 Hz) 7.32-7.49 (2H, m) 7.56-7.65 (2H, m) 7.77 (1H, d, J=8.5 Hz) 7.94 (1H, d, J=1.5 Hz) 8.46-8.51 (1H, m).

Workup

  1. temperatureAfter cooling to rt the mixture
  2. concentrationwas concentrated in vacuo
  3. dissolutionThe residue was dissolved in DCM (100 mL)
  4. washwashed with water (2×40 mL)
  5. dry with materialThe organic layer was dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by prep-HPLC (Table 2, Method a,)

Sources & evidence

ORD record
ord-e59229192b604aa8a5858415036dadaa
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

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