Sodium Hydroxide → HCID 178525668, compound

HRID 1485362Notes

Reaction equation

HRID 1485362 reaction equation
CS([C:5]1[N:6]=[C:7]([NH:26][C:27]2[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][CH:28]=2)[C:8]2[CH2:14][CH2:13][N:12]([C:15]3[C:20]([C:21]([F:24])([F:23])[F:22])=[CH:19][CH:18]=[CH:17][N:16]=3)[CH2:11][CH2:10][C:9]=2[N:25]=1)(=O)=O.[OH-:37].[Na+].[OH2:39].[O:40]1CCOCC1>C(O)(C(F)(F)F)=O>[F:22][C:21]([F:24])([F:23])[C:20]([OH:39])=[O:37].[F:34][C:33]([F:36])([F:35])[C:30]1[CH:31]=[CH:32][C:27]([NH:26][C:7]2[C:8]3[CH2:14][CH2:13][N:12]([C:15]4[C:20]([C:21]([F:24])([F:23])[F:22])=[CH:19][CH:18]=[CH:17][N:16]=4)[CH2:11][CH2:10][C:9]=3[N:25]=[C:5]([OH:40])[N:6]=2)=[CH:28][CH:29]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 218864351,4-Dioxane--water (1/1)HCID 58972737HCID 58972737, compound

Product 1

HCID 178525668HCID 178525668, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidCatalyst

Procedure

A solution of [2-methanesulfonyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine (Example 53; 112 mg, 0.21 mmol) and NaOH (25 mg, 0.63 mmol) in 1:3 H2O/dioxane (4 mL) was heated at 60° C. for 1 h. The mixture was cooled, acidified with TFA (3 drops), and directly purified using Preparative HPLC (conditions as in Example 54) to give the title compound (60 mg, 98%). MS (ESI): mass calcd. for C21H17F6N5O, 469.13; m/z found, 470.5 [M+H]+. 1H NMR (CDCl3): 8.46-8.41 (m, 1H), 7.97 (dd, J=7.8, 1.5 Hz, 1H), 7.64 (s, 4H), 7.09 (dd, J=7.7, 4.9 Hz, 1H), 3.63-3.58 (m, 2H), 3.58-3.53 (m, 2H), 3.18-3.12 (m, 2H), 2.89-2.84 (m, 2H).

Workup

  1. temperatureThe mixture was cooled
  2. customdirectly purified

Sources & evidence

ORD record
ord-2e3b2b086c804cfbb83f69f02f21186a
Source dataset
uspto-grants-2016_08
Patent number
US09422293B2

Reaction notes

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