HCID 58972733, compound → HCID 24784683, compound

HRID 1485354Notes

Reaction equation

HRID 1485354 reaction equation
[CH3:1][Mg]Br.[N:4]1([C:10]2[N:11]=[C:12]([NH:31][C:32]3[CH:37]=[CH:36][C:35]([C:38](=[O:40])[CH3:39])=[CH:34][CH:33]=3)[C:13]3[CH2:19][CH2:18][N:17]([C:20]4[C:25]([C:26]([F:29])([F:28])[F:27])=[CH:24][CH:23]=[CH:22][N:21]=4)[CH2:16][CH2:15][C:14]=3[N:30]=2)[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1>CCOCC.C1COCC1>[N:4]1([C:10]2[N:11]=[C:12]([NH:31][C:32]3[CH:33]=[CH:34][C:35]([C:38]([OH:40])([CH3:1])[CH3:39])=[CH:36][CH:37]=3)[C:13]3[CH2:19][CH2:18][N:17]([C:20]4[C:25]([C:26]([F:27])([F:28])[F:29])=[CH:24][CH:23]=[CH:22][N:21]=4)[CH2:16][CH2:15][C:14]=3[N:30]=2)[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1

Participants

5

Reactant 2

HCID 58972733HCID 58972733, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 24784683HCID 24784683, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of methylmagnesium bromide (170 mL of a 3.0 M solution in Et2O, 0.51 mmol) in THF at 0° C. was added a solution of 1-[4-({2-piperidin-1-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl}amino)phenyl]ethanone (Example 156; 59.8 mg, 0.117 mmol) in THF. The solution was allowed to warm to rt over 1 h, and stirred at rt for an additional 5 min. The reaction mixture was then quenched with satd. aq. NH4Cl and extracted with EtOAc. The organic layers were combined, dried, and concentrated. The crude residue was purified (FCC) to give the title compound (51 mg, 83%). MS (ESI): mass calcd. for C28H33F3N6O, 526.27; m/z found, 527.3 [M+H]+. 1H NMR (CDCl3): 8.39-8.37 (m, 1H), 7.86 (dd, J=7.8, 1.8 Hz, 1H), 7.55-7.51 (m, 2H), 7.46-7.41 (m, 2H), 6.94-6.90 (m, 1H), 6.35 (s, 1H), 3.77-3.69 (m, 4H), 3.63-3.53 (m, 4H), 3.10-3.03 (m, 2H), 2.87-2.80 (m, 2H), 1.70 (s, 1H), 1.66-1.60 (m, 6H), 1.54 (s, 6H).

Workup

  1. customThe reaction mixture was then quenched with satd
  2. extractionaq. NH4Cl and extracted with EtOAc
  3. customdried
  4. concentrationconcentrated
  5. customThe crude residue was purified (FCC)

Sources & evidence

ORD record
ord-8dae080fe8a3439191f5347a5ed57751
Source dataset
uspto-grants-2016_08
Patent number
US09422293B2

Reaction notes

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