Sodium Hydroxide → HCID 67279057, compound

HRID 1943286Notes

Reaction equation

HRID 1943286 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:14]2([OH:21])[CH2:17][CH:16]([C:18](O)=[O:19])[CH2:15]2)[CH:5]=[CH:6][C:7]=1[CH2:8][N:9]1[CH2:13][CH2:12][CH2:11][CH2:10]1.[CH3:22][NH:23][CH2:24][C:25]1[C:30]([CH3:31])=[CH:29][CH:28]=[CH:27][N:26]=1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.[OH-].[Na+]>CCOC(C)=O>[CH3:22][N:23]([CH2:24][C:25]1[C:30]([CH3:31])=[CH:29][CH:28]=[CH:27][N:26]=1)[C:18]([CH:16]1[CH2:15][C:14]([C:4]2[CH:5]=[CH:6][C:7]([CH2:8][N:9]3[CH2:10][CH2:11][CH2:12][CH2:13]3)=[C:2]([Cl:1])[CH:3]=2)([OH:21])[CH2:17]1)=[O:19]

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 111923Propylphosphonic anhydrideHCID 23365109N-Methyl-1-(3-methylpyridin-2-yl)methanamineHCID 574858713-(3-Chloro-4-((pyrrolidin-1-yl)methyl)phenyl)-3-hydroxycyclobutanecarboxylic acid

Product 1

HCID 67279057HCID 67279057, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of crude intermediate 17, 3-(3-chloro-4-((pyrrolidin-1-yl)methyl)phenyl)-3-hydroxycyclobutanecarboxylic acid (˜4.3 mL ˜0.65 mmol) was added methyl-(3-methyl-pyridin-2-ylmethyl)-amine (176 mg, 1.29 mmol) and T3P (50% solution in EtOAc, 0.62 ml, 0.97 mmol). The resulting reaction mixture was stirred at RT for 1 hr and then 25 ml of 1N NaOH and 100 ml of EtOAc were added and the layers were separated. The aqueous layer was subjected to EtOAc extraction (2×60 ml) again and the combined organic layers were dried over MgSO4 and evaporated. The residue was purified by flash column chromatography using a 40 g ISCO™ column, eluting with 5% MeOH/CH2Cl2 containing 0.25% NH4OH. The product containing fractions were collected and concentrated under reduced pressure to give the title compound 127 mg, 46% yield). Rf=0.30 (15% MeOH/CH2Cl2+0.2% NH4OH); LRMS m/z Calcd for C24H30Cl N3 O2, 427.9, found, 428.2 (M+1) APCI; 400 MHz 1H NMR (CDCl3) 2:1 mixture of rotomers, diagnostic peaks, δ 4.72, 4.53 (s, 2H), 3.72 & 3.70 (s, 2H), 2.97, 2.93 (s, 3H), 1.76-1.74 (m, 4H); 100 MHz 13C NMR (CDCl3) 2:1 mixture of rotomers, diagnostic peaks δ 177.6, 175.7, 154.7, 153.6, 146.8, 146.6, 126.5, 126.4, 122.8, 122.7, 73.4, 73.2, 56.7, 56.6, 54.3, 54.2, 51.1, 41.4, 40.9, 35.6, 35.4, 28.9, 28.7, 23.7, 23.6, 18.3, 18.2.

Workup

  1. customThe resulting reaction mixture
  2. customthe layers were separated
  3. extractionThe aqueous layer was subjected to EtOAc extraction (2×60 ml) again
  4. dry with materialthe combined organic layers were dried over MgSO4
  5. customevaporated
  6. customThe residue was purified by flash column chromatography
  7. washeluting with 5% MeOH/CH2Cl2 containing 0.25% NH4OH
  8. additionThe product containing fractions
  9. customwere collected
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-773a5698d28b4930af3506ced27b8037
Source dataset
uspto-grants-2013_03
Patent number
US08389743B2

Reaction notes

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