Sodium hydride → HCID 57911435, compound

HRID 1666153Notes

Reaction equation

HRID 1666153 reaction equation
[C:1]([NH:5][C:6]1[N:11]=[C:10]2[C@H:12]([OH:25])[CH2:13][CH2:14][C@@H:15]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:18]=3[F:24])[CH2:16][C:9]2=[CH:8][CH:7]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].C(N(CC)CC)C.[O:35]=[C:36]1[NH:44][C:39]2=[N:40][CH:41]=[CH:42][CH:43]=[C:38]2[N:37]1[CH:45]1[CH2:50][CH2:49][N:48]([C:51](OC2C=CC([N+]([O-])=O)=CC=2)=[O:52])[CH2:47][CH2:46]1>C1COCC1>[O:35]=[C:36]1[NH:44][C:39]2=[N:40][CH:41]=[CH:42][CH:43]=[C:38]2[N:37]1[CH:45]1[CH2:46][CH2:47][N:48]([C:51]([O:25][C@H:12]2[C:10]3=[N:11][C:6]([NH:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[CH:7][CH:8]=[C:9]3[CH2:16][C@H:15]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:18]=3[F:24])[CH2:14][CH2:13]2)=[O:52])[CH2:49][CH2:50]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 57911483HCID 57911483, compound2×HCID 86635016HCID 86635016, compound

Product 1

HCID 57911435HCID 57911435, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(6R,9R)-2-(tert-butylamino)-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ol (69.1 mg, 0.199 mmol) with stirring bar was azeotroped by benzene. Sodium hydride (47.9 mg, 1.995 mmol) was added to the THF (3 mL) suspension of (6R,9R)-2-(tert-butylamino)-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ol (69.1 mg, 0.199 mmol) and 4-nitrophenyl 4-(2-oxo-2,3-dihydro-1H-imidazo [4,5-b]pyridin-1-yl)piperidine-1-carboxylate compound with triethylamine (1:3) trihydrochloride (238 mg, 0.299 mmol) at rt. The reaction was stirred at room temperature overnight. The reaction was quenched by water and partitioned between ethyl acetate and water. The ethyl acetate layer was washed by water twice before dried (Na2SO4), filtered and concentrated. Flash column by methanol in CH2Cl2 from 0 to 10% gave the desired product as a white solid. The product was further purified by prep HPLC (69.2 mg, 26%). 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 8.07 (d, J=5.19 Hz, 1H) 7.34-7.44 (m, 1H) 6.96-7.15 (m, 4H) 6.08-6.28 (m, 1H) 5.83-5.99 (m, 1H) 4.42-4.77 (m, 3H) 3.16-3.25 (m, 1H) 2.86-3.14 (m, 3H) 2.62-2.72 (m, 1H) 2.11-2.38 (m, 5H) 1.94 (d, J=11.90 Hz, 3H) 1.52-1.60 (m, 1H) 1.46 (s, 9H).

Workup

  1. customwas azeotroped by benzene
  2. customThe reaction was quenched by water
  3. custompartitioned between ethyl acetate and water
  4. washThe ethyl acetate layer was washed by water twice
  5. dry with materialbefore dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-0a7afc67cbf24398b6148664796c1172
Source dataset
uspto-grants-2011_10
Patent number
US08044043B2

Reaction notes

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