Hydrochloric Acid → HCID 178508902, compound

HRID 1740371Notes

Reaction equation

HRID 1740371 reaction equation
Cl.[NH2:2][C:3]([NH2:5])=[NH:4].CC(C)([O-:9])C.[K+].S=[C:13]1[CH:18]([CH2:19]C)[CH2:17][C@@H:16]([CH2:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([Br:29])=[CH:25][CH:24]=2)[CH2:15][N:14]1C(O)=O.Cl>C(O)C>[NH2:4][C:3]1[N:5]=[C:19]([OH:9])[C:18]2[CH2:17][C@@H:16]([CH2:21][CH2:22][C:23]3[CH:28]=[CH:27][C:26]([Br:29])=[CH:25][CH:24]=3)[CH2:15][NH:14][C:13]=2[N:2]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 5742Guanidine HydrochlorideHCID 23665647Potassium tert-butoxideHCID 86749225HCID 86749225, compound

Product 1

HCID 178508902HCID 178508902, compoundYield 80.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
90 °C

Procedure

A suspension of 740 mg (7.77 mmol) of guanidine hydrochloride in 5 mL of ethanol was neutralized by addition of 950 mg (7.77 mmol) of potassium tert-butoxide. The precipitated potassium chloride was filtered with filter aid and washed with an additional 5 mL of ethanol. A solution of 720 mg (1.94 mmol) of (3RS,5R)-2-thioxo-3-ethylcarboxy-5-[2-(4-bromophenyl)ethyl]piperidine in 5 mL ethanol was added to the filtrate and this solution was reduced to a volume of 2-3 mL under vacuum. The solution was heated in an oil bath (T=90° C.) under a stream of nitrogen for 2 h. After cooling to ambient temperature, the mixture was subjected to further vacuum evaporation. The resulting solid was suspended in water, sonicated to form a uniform suspension, and neutralized to pH 7 by addition of 1N aq. HCl. The resulting suspension was heated to about 90° C. for 15 min, then cooled to ambient temp. and filtered. The product was dried in vacuo (10 torr), affording 544 mg (80%) of (R)-(-)-2-amino-4-hydroxy-6-[2-(4-bromophenyl)ethyl]-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine mp 275°-283° C., [α]589 -30.9° (c 1, DMF), 1H NMR (DMSO-d6) δ 9.70 (bs, 1H), 7.40 (d, J=8.3 Hz, 2H), 7.12 (d, J=8.3 Hz, 2H), 6.23 (d, J=8.3 Hz, 2H), 5.96 (s, 2H), 3.15 (bd, J=11 Hz, 1H), 2.45 (m, 2H), 1.78 (dd, J=8.6, 15.1, 1H), 1.50 (m, 3H); IR (KBr) 3400, 3343, 1678, 1642 cm-1 ; MS (EI), m/z 350 (78), 348 (72), 166 (100), 165 (95), 164 (31), 151 (68), 139 (19). The NMR spectrum was identical with that of a sample of (S)-(+)-3 obtained as described in U.S. Pat. No. 5,008,391.

Workup

  1. filtrationThe precipitated potassium chloride was filtered
  2. filtrationwith filter aid
  3. washwashed with an additional 5 mL of ethanol
  4. temperatureAfter cooling to ambient temperature
  5. customthe mixture was subjected to further vacuum evaporation
  6. customsonicated
  7. customto form a uniform suspension
  8. temperatureThe resulting suspension was heated to about 90° C. for 15 min
  9. temperaturecooled to ambient temp.
  10. filtrationfiltered
  11. customThe product was dried in vacuo (10 torr)

Sources & evidence

ORD record
ord-e0347e02717249aba3f422aad9ce8e6d
Source dataset
uspto-grants-1999_10
Patent number
US05969136

Reaction notes

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