Piperidine-1-carboximidamide Hydrobromide → Jnj-38893777

HRID 1485343노트

반응식

HRID 1485343 반응식
[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

참가 물질

6

반응물 4

HCID 2777304Piperidine-1-carboximidamide HydrobromideHCID 23665647Potassium tert-butoxideHCID 589727845-Oxo-1-(3-trifluoromethyl-pyridin-2-yl)-azepane-4-carboxylic acid ethyl ester2회HCID 178517884HCID 178517884, 화합물

생성물 1

HCID 16742146Jnj-38893777수율 51%

시약·촉매·용매 1

HCID 6386tert-Butanol용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-44831f8d2d7a4bf3a38f3a74ad24dc53
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09422293B2

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