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 1747127ノート

反応式

HRID 1747127 の反応式
[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

参加物

5

反応物 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、化合物

生成物 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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-bc819346354d4653a8b6366aaaaaf187
出典データセット
uspto-grants-2015_10
特許番号
US09150532B2

反応ノート

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