Azobisisobutyronitrile → tert-butyl ((3aS,5S,6aR)-3a-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)hexahydro-2H-cyclopenta[b]furan-5-yl)carbamate

HRID 1747122Notes

Reaction equation

HRID 1747122 reaction equation
C1([Se][C@@H:8]2[C@H:12]3[O:13][CH2:14][CH2:15][C@@:11]3([C:16]([N:18]3[CH2:27][CH2:26][C:25]4[N:24]=[CH:23][C:22]([C:28]([F:31])([F:30])[F:29])=[CH:21][C:20]=4[CH2:19]3)=[O:17])[CH2:10][C@@H:9]2[NH:32][C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36])C=CC=CC=1.C[Si]([SiH]([Si](C)(C)C)[Si](C)(C)C)(C)C.CC(N=NC(C#N)(C)C)(C#N)C>C1C=CC=CC=1>[F:31][C:28]([F:29])([F:30])[C:22]1[CH:23]=[N:24][C:25]2[CH2:26][CH2:27][N:18]([C:16]([C@:11]34[CH2:10][C@H:9]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:37])([CH3:38])[CH3:36])[CH2:8][C@H:12]3[O:13][CH2:14][CH2:15]4)=[O:17])[CH2:19][C:20]=2[CH:21]=1

Participants

5

Reactant 3

HCID 6547AzobisisobutyronitrileHCID 123134Tris(trimethylsilyl)silaneHCID 86708131tert-butyl ((3aS,5S,6S,6aS)-6-(phenylselanyl)-3a-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)hexahydro-2H-cyclopenta[b]furan-5-yl)carbamate

Product 1

HCID 86708132tert-butyl ((3aS,5S,6aR)-3a-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)hexahydro-2H-cyclopenta[b]furan-5-yl)carbamate

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

To a solution of the product of Step E (1.51 g, 2.67 mmol, 1 eq), tris(trimethylsilyl)silane (1.72 mL, 5.34 mmol, 2 eq) and AIBN (438 mg, 2.67 mmol, 1 eq) in benzene (20 mL) was warmed to 80° C. under Ar. After 3 hrs, the solution was concentrated. Purification by chromatography (80 g column) eluting with 50 to 100% EtOAc/heptane afforded the title compound of Step F. 1H NMR (CHLOROFORM-d) δ: 8.72 (br. s., 1H), 7.71 (br. s., 1H), 4.97-5.09 (m, 1H), 4.70-4.91 (m, 2H), 4.56-4.69 (m, 1H), 4.28 (br. s., 1H), 3.80-4.07 (m, 3H), 3.71 (q, J=7.3 Hz, 1H), 3.13 (br. s., 2H), 2.07-2.53 (m, 4H), 1.81 (br. s., 1H), 1.61-1.72 (m, 1H), 1.40 (s, 9H). Calculated for C22H28F3N3O4: 478.2 (M+23). found: 478.2.

Workup

  1. concentrationthe solution was concentrated
  2. customPurification by chromatography (80 g column)
  3. washeluting with 50 to 100% EtOAc/heptane

Sources & evidence

ORD record
ord-29a10ce14dd940388d95a3ba554ecdf2
Source dataset
uspto-grants-2015_10
Patent number
US09150532B2

Reaction notes

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