Tetrahydrofuran → HCID 24784927, compound

HRID 1485357Notes

Reaction equation

HRID 1485357 reaction equation
[CH3:1][C:2]([C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15]2[C:25]3[CH2:24][CH2:23][N:22]([C:26]4[C:31]([C:32]([F:35])([F:34])[F:33])=[CH:30][CH:29]=[CH:28][N:27]=4)[CH2:21][CH2:20][C:19]=3[N:18]=[C:17]([CH:36]([CH3:38])[CH3:37])[N:16]=2)=[CH:10][CH:9]=1)([CH3:7])[C:3]([O:5]C)=[O:4].C1COCC1.O.[OH-].[Li+]>O>[CH3:7][C:2]([C:8]1[CH:9]=[CH:10][C:11]([NH:14][C:15]2[C:25]3[CH2:24][CH2:23][N:22]([C:26]4[C:31]([C:32]([F:34])([F:35])[F:33])=[CH:30][CH:29]=[CH:28][N:27]=4)[CH2:21][CH2:20][C:19]=3[N:18]=[C:17]([CH:36]([CH3:38])[CH3:37])[N:16]=2)=[CH:12][CH:13]=1)([CH3:1])[C:3]([OH:5])=[O:4]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 24784681HCID 24784681, compound

Product 1

HCID 24784927HCID 24784927, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of methyl 2-methyl-2-[4-({2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl}amino)phenyl]propanoate (Example 174; 63 mg, 0.12 mmol) in 1:2 THF:H2O (3 mL:6 mL) was added lithium hydroxide monohydrate (8.0 mg, 0.19 mmol). The mixture was heated at 60° C. for 5 h. The THF was removed under reduced pressure, and the resulting solution was acidified to neutral pH with 10% aq. HCl. The solution was then extracted with EtOAc. The organic layers were combined, dried, and concentrated. The crude residue was purified (FCC) to give the title compound (37 mg, 60%). MS (ESI): mass calcd. for C27H30F3N5O2, 513.24; m/z found, 514.1 [M+H]+. 1H NMR (CD3OD): 8.45-8.42 (m, 1H), 8.01 (dd, J=7.9, 1.7 Hz, 1H), 7.69-7.63 (m, 2H), 7.38-7.33 (m, 2H), 7.13-7.09 (m, 1H), 3.57-3.50 (m, 4H), 3.21-3.16 (m, 2H), 3.13-3.08 (m, 2H), 3.01-2.93 (m, 1H), 1.57 (s, 6H), 1.28 (d, J=6.9 Hz, 6H).

Workup

  1. customThe THF was removed under reduced pressure
  2. extractionThe solution was then extracted with EtOAc
  3. customdried
  4. concentrationconcentrated
  5. customThe crude residue was purified (FCC)

Sources & evidence

ORD record
ord-23b41042f2ba432a96c860727df3a435
Source dataset
uspto-grants-2016_08
Patent number
US09422293B2

Reaction notes

Loading…