Methanol → HCID 136348443, compound

HRID 1748776Notes

Reaction equation

HRID 1748776 reaction equation
[CH2:1]([N:3]1[C:7]2[NH:8][CH2:9][CH2:10][S:11][CH:12]([C:13]3[CH:23]=[CH:22][C:16]([C:17]([O:19]CC)=[O:18])=[CH:15][C:14]=3[CH3:24])[C:6]=2[C:5]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=2)=[N:4]1)[CH3:2].[OH-].[Na+].C1COCC1.CO>O>[CH2:1]([N:3]1[C:7]2[NH:8][CH2:9][CH2:10][S:11][CH:12]([C:13]3[CH:23]=[CH:22][C:16]([C:17]([OH:19])=[O:18])=[CH:15][C:14]=3[CH3:24])[C:6]=2[C:5]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=2)=[N:4]1)[CH3:2]

Participants

6

Reactant 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 136348445HCID 136348445, compound

Product 1

HCID 136348443HCID 136348443, compoundYield 96.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of ethyl 4-(1-ethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylbenzoate (5.0 g, 11.8 mmol, prepared using B from Example #2, Step A with ethyl hydrazine oxalate, C with 4-bromo-2-methylbenzaldehyde (Asta Tech) and 2-mercaptoacetic, D with borane-THF complex, E with PdCl2(dppf), TEA, DMF and EtOH), NaOH (0.95 g, 23.6 mmol), THF (30 mL), MeOH (30 mL) and water (15 mL) was stirred at rt for about 3 h. The organic volatiles were removed under reduced pressure. The aqueous layer was adjusted to about pH 6 by the addition of 1N aqueous HCl. The precipitate was collected by filtration and dried under reduced pressure to afford 4-(1-ethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylbenzoic acid (4.5 g, 11.4 mmol, 96%) as a white solid. LC-MS (Table 1, Method 1) Rt=1.15 min, m/z 395 (M+H)+.

Workup

  1. customThe organic volatiles were removed under reduced pressure
  2. additionThe aqueous layer was adjusted to about pH 6 by the addition of 1N aqueous HCl
  3. filtrationThe precipitate was collected by filtration
  4. customdried under reduced pressure

Sources & evidence

ORD record
ord-4b350fbb61af4b079f6b4aa779cc3e7f
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

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