Sodium Hydroxide → 4-amino-1-(2'-amino-6',7'-dihydro-5'H-spiro[cyclopentane-1,8'-quinazoline]-4'-yl)piperidine-4-carboxylic acid

HRID 2059754Notes

Reaction equation

HRID 2059754 reaction equation
[NH2:1][C:2]1([C:23]([O:25]C)=[O:24])[CH2:7][CH2:6][N:5]([C:8]2[C:17]3[CH2:16][CH2:15][CH2:14][C:13]4([CH2:21][CH2:20][CH2:19][CH2:18]4)[C:12]=3[N:11]=[C:10]([NH2:22])[N:9]=2)[CH2:4][CH2:3]1.[OH-].[Na+]>CO>[NH2:1][C:2]1([C:23]([OH:25])=[O:24])[CH2:3][CH2:4][N:5]([C:8]2[C:17]3[CH2:16][CH2:15][CH2:14][C:13]4([CH2:21][CH2:20][CH2:19][CH2:18]4)[C:12]=3[N:11]=[C:10]([NH2:22])[N:9]=2)[CH2:6][CH2:7]1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 44231854methyl 4-amino-1-(2'-amino-6',7'-dihydro-5'H-spiro[cyclopentane-1,8'-quinazoline]-4'-yl)piperidine-4-carboxylate

Product 1

HCID 442316214-amino-1-(2'-amino-6',7'-dihydro-5'H-spiro[cyclopentane-1,8'-quinazoline]-4'-yl)piperidine-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of the product from Example 11 (30 mg, 0.083 mmol) in MeOH (5 mL) was treated with NaOH solution (1 mL, 10%) and stirred for 16 hours. The mixture was concentrated under reduced pressure, and the resulting oil was chromatographed on silica gel (6:1:1 EtOAc/HCO2H/H2O, eluant). The fractions containing the still-impure product were combined and concentrated under reduced pressure, then the residue was again chromatographed on silica gel, this time eluting with NH4OH/MeOH/CH2Cl2 (1.5:13.5:85), to provide the title product. 1H NMR (300 MHz, CD3OD) δ 3.70-3.81 (m, 2 H), 3.45-3.57 (m, 2 H), 2.52 (t, J=5.43 Hz, 2 H), 2.25-2.36 (m, 2 H), 1.98-2.09 (m, 2 H), 1.76-1.94 (m, 6 H), 1.61-1.74 (m, 6 H). MS (DCI+) m/z 346 (M+H) and 368 (M+Na).

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customthe resulting oil was chromatographed on silica gel (6:1:1 EtOAc/HCO2H/H2O, eluant)
  3. additionThe fractions containing the still-impure product
  4. concentrationconcentrated under reduced pressure
  5. customthe residue was again chromatographed on silica gel
  6. washthis time eluting with NH4OH/MeOH/CH2Cl2 (1.5:13.5:85)

Sources & evidence

ORD record
ord-4cbf8419f0834406ae56346e5505f272
Source dataset
uspto-grants-2012_10
Patent number
US08278313B2

Reaction notes

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