Ammonium Chloride → tert-butyl ((1S,4S)-4-(2-cyclopropyl-2-hydroxyethyl)-4-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)cyclopent-2-en-1-yl)carbamate

HRID 1747127Notes

Reaction equation

HRID 1747127 reaction equation
[CH:1]1([Mg]Br)[CH2:3][CH2:2]1.[O:6]=[CH:7][CH2:8][C@@:9]1([C:22]([N:24]2[CH2:33][CH2:32][C:31]3[N:30]=[CH:29][C:28]([C:34]([F:37])([F:36])[F:35])=[CH:27][C:26]=3[CH2:25]2)=[O:23])[CH2:13][C@H:12]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH:11]=[CH:10]1.[NH4+].[Cl-]>C1COCC1>[CH:1]1([CH:7]([OH:6])[CH2:8][C@@:9]2([C:22]([N:24]3[CH2:33][CH2:32][C:31]4[N:30]=[CH:29][C:28]([C:34]([F:35])([F:36])[F:37])=[CH:27][C:26]=4[CH2:25]3)=[O:23])[CH2:13][C@H:12]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH:11]=[CH:10]2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 86708134tert-butyl ((1S,4S)-4-(2-oxoethyl)-4-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)cyclopent-2-en-1-yl)carbamateHCID 178418630HCID 178418630, compound

Product 1

HCID 86708135tert-butyl ((1S,4S)-4-(2-cyclopropyl-2-hydroxyethyl)-4-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)cyclopent-2-en-1-yl)carbamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of cyclopropyl magnesium bromide (6.88 mL of a 0.5 M solution in THF, 3.44 mmol, 8 eq) in THF (5 mL) at 0° C. under Ar was added a solution of the product of Step A (195 mg, 0.43 mmol, 1 eq) in THF (17 mL) dropwise over 30 min. After 45 min, saturated NH4Cl was added, the solution extracted with ethyl acetate, the organics combined, dried over MgSO4 and concentrated. Purification by chromatography (12 g column) eluting with 30 to 100% EtOAc/heptane afforded the title compound of Step B as a mix of diastereomers. 1H NMR (CHLOROFORM-d) δ: 8.70 (br. s., 1H), 7.70 (br. s., 1H), 6.11-6.42 (m, 1H), 5.77 (t, J=5.1 Hz, 1H), 4.81 (d, J=12.2 Hz, 4H), 4.03 (dt, J=12.8, 6.2 Hz, 1H), 3.81-3.98 (m, 1H), 3.59-3.75 (m, 2H), 3.03-3.25 (m, 2H), 2.69-3.00 (m, 2H), 2.19-2.67 (m, 3H), 1.91-2.18 (m, 3H), 1.55-1.88 (m, 5H), 1.42 (s, 9H), 0.88-0.99 (m, 1H), 0.42-0.56 (m, 2H), 0.14-0.35 (m, 2H). Calculated for C25H32F3N3O4: 496.2 (M+1). found: 496.2.

Workup

  1. extractionthe solution extracted with ethyl acetate
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. customPurification by chromatography (12 g column)
  5. washeluting with 30 to 100% EtOAc/heptane

Sources & evidence

ORD record
ord-bc819346354d4653a8b6366aaaaaf187
Source dataset
uspto-grants-2015_10
Patent number
US09150532B2

Reaction notes

Loading…