Methanol → HCID 71711673, compound

HRID 470938Notes

Reaction equation

HRID 470938 reaction equation
[C:1]([O:5][CH:6]([C:10]1[C:11]([CH:29]([CH3:31])[CH3:30])=[N:12][C:13]2[C:14]([CH3:28])([CH3:27])[CH2:15][NH:16][CH2:17][C:18]=2[C:19]=1[C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC.[CH3:39][C:40]1[CH:45]=[CH:44][C:43]([S:46]([NH:49][CH:50]([CH2:54][C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[C:51](Cl)=[O:52])(=[O:48])=[O:47])=[CH:42][CH:41]=1.CO>C(Cl)Cl>[C:1]([O:5][CH:6]([C:10]1[C:11]([CH:29]([CH3:31])[CH3:30])=[N:12][C:13]2[C:14]([CH3:28])([CH3:27])[CH2:15][N:16]([C:51](=[O:52])[CH:50]([NH:49][S:46]([C:43]3[CH:42]=[CH:41][C:40]([CH3:39])=[CH:45][CH:44]=3)(=[O:48])=[O:47])[CH2:54][C:55]3[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=3)[CH2:17][C:18]=2[C:19]=1[C:20]1[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 887MethanolHCID 8471TriethylamineHCID 4093506HCID 4093506, compoundHCID 717115302-Tert-butoxy-2-(4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)acetic acid

Product 1

HCID 71711673HCID 71711673, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-tert-butoxy-2-(4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)acetic acid (example 1) (10 mg, 0.023 mmol) in CH2Cl2 (5 mL) was added Et3N (0.020 mL, 0.140 mmol) and the resulting mixture cooled to 0° C. Added to this was 2-(4-methylphenylsulfonamido)-3-phenylpropanoyl chloride (23.65 mg, 0.070 mmol) and the mixture stirred at room temperature (mixture became a clear colorless solution over time). After 1 h, 0.5 mL MeOH was added and the mixture was concentrated under a stream of air and taken up in MeOH and purified by preparative HPLC (10% AcCN/90% H2O/0.1% NH4OAc, Sunfire 19×100 mm, C18, 5 μm column) The product-containing fractions were concentrated to remove the organic solvent and the resulting precipitate was collected by filtration to give 2-tert-butoxy-2-(4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-6-(2-(4-methylphenylsulfonamido)-3-phenylpropanoyl)-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)acetic acid (3.7 mg, 21% yield) as a white solid. 1H NMR (400 MHz, CD3OD) δ ppm 7.56-7.80 (1H, m), 6.91-7.57 (12H, m), 6.71-6.92 (1H, m), 4.85 (1H, s), 3.99-4.26 (1H, m), 3.78-4.00 (0.5H, m), 3.46-3.77 (1.5H, m), 3.36-3.46 (2H, m), 3.13-3.28 (1H, m), 2.60-2.87 (2H, m), 2.11-2.50 (3H, m), 0.85-1.46 (21H, m). 19F NMR (400 MHz, CD3OD) δ ppm −114.16, −115.11, −117.98, −118.41. LCMS (M+H) calcd for C41H49FN3O6: 730.33. found: 730.03.

Workup

  1. concentrationthe mixture was concentrated under a stream of air
  2. custompurified by preparative HPLC (10% AcCN/90% H2O/0.1% NH4OAc, Sunfire 19×100 mm, C18, 5 μm column) The product-containing fractions
  3. concentrationwere concentrated
  4. customto remove the organic solvent
  5. filtrationthe resulting precipitate was collected by filtration

Sources & evidence

ORD record
ord-253451cb3444450ab4163c174641fb31
Source dataset
uspto-grants-2014_01
Patent number
US08629276B2

Reaction notes

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