Piperidine-1-carboximidamide Hydrobromide → Jnj-38893777

HRID 1485343Notes

Reaction equation

HRID 1485343 reaction equation
[N:1]1([C:7]2[N:8]=[C:9](O)[C:10]3[CH2:16][CH2:15][N:14]([C:17]4[C:22]([C:23]([F:26])([F:25])[F:24])=[CH:21][CH:20]=[CH:19][N:18]=4)[CH2:13][CH2:12][C:11]=3[N:27]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:29]C([O-])(C)C.[K+].C(OC(C1C(=O)CCN([C:48]2[C:53]([C:54]([F:57])([F:56])[F:55])=[CH:52][CH:51]=[CH:50][N:49]=2)CC1)=O)C.Br.N1(C(=N)N)CCCCC1>CC(O)(C)C>[N:1]1([C:7]2[N:8]=[C:9]([NH:49][C:50]3[CH:51]=[CH:52][C:53]([C:54]([F:55])([F:56])[F:57])=[CH:48][CH:29]=3)[C:10]3[CH2:16][CH2:15][N:14]([C:17]4[C:22]([C:23]([F:26])([F:25])[F:24])=[CH:21][CH:20]=[CH:19][N:18]=4)[CH2:13][CH2:12][C:11]=3[N:27]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 2777304Piperidine-1-carboximidamide HydrobromideHCID 23665647Potassium tert-butoxideHCID 589727845-Oxo-1-(3-trifluoromethyl-pyridin-2-yl)-azepane-4-carboxylic acid ethyl ester2×HCID 178517884HCID 178517884, compound

Product 1

HCID 16742146Jnj-38893777Yield 51%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Procedure

2-Piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ol. To solution of KOtBu (1.3 g, 5.77 mmol) in tBuOH (32 mL) was added 5-oxo-1-(3-trifluoromethyl-pyridin-2-yl)-azepane-4-carboxylic acid ethyl ester (Intermediate B; 1.27 g, 3.85 mmol), followed by piperidine-1-carboximidamide hydrobromide (1.2 g, 5.77 mmol). After heating at reflux for 24 h, the mixture was cooled and concentrated. The residue was dissolved in water and CH2Cl2. The aqueous layer was acidified to pH=7 with HOAc. The layers were separated and the aqueous layer was extracted with CH2Cl2. The combined organic layers were dried (Na2SO4) and concentrated. The residue was triturated with Et2O and filtered. The filtrate was concentrated and the residue was purified (FCC) to give the title compound (776.4 g, 51%—combined filtered and chromatographed).

Workup

  1. temperatureAfter heating
  2. temperatureat reflux for 24 h
  3. temperaturethe mixture was cooled
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in water
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with CH2Cl2
  8. dry with materialThe combined organic layers were dried (Na2SO4)
  9. concentrationconcentrated
  10. customThe residue was triturated with Et2O
  11. filtrationfiltered
  12. concentrationThe filtrate was concentrated
  13. customthe residue was purified (FCC)

Sources & evidence

ORD record
ord-44831f8d2d7a4bf3a38f3a74ad24dc53
Source dataset
uspto-grants-2016_08
Patent number
US09422293B2

Reaction notes

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