HCID 10293956, compound → HCID 69662788, compound

HRID 1830850Notes

Reaction equation

HRID 1830850 reaction equation
[NH2:1][CH2:2][C:3]1[N:8]=[C:7]2[S:9][C:10]3[CH2:15][S:14](=[O:16])[CH2:13][CH2:12][C:11]=3[C:6]2=[C:5]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)[C:4]=1[Cl:25]>CO>[NH2:1][CH2:2][C:3]1[N:8]=[C:7]2[S:9][C:10]3[CH2:15][S@@:14](=[O:16])[CH2:13][CH2:12][C:11]=3[C:6]2=[C:5]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)[C:4]=1[Cl:25]

Participants

3

Reactant 1

HCID 10293956HCID 10293956, compound

Product 1

HCID 69662788HCID 69662788, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

To methanol heated to 60° C. (63 L) was added 2-(aminomethyl)-3-chloro-4-(4-methoxyphenyl)-7-oxido-5,8-dihydro-6H-thiopyrano[4′,3′:4,5]thieno[2,3-b]pyridine (6.5 kg) and the mixture was stirred for 5 minutes, followed by addition of (R)-(−)-hydrogenphosphate-1,1′-bihaphthyl-2,2′-diyl (3.455 kg). The mixture was stirred at 60° C. for 10 minutes, slowly cooled to 25° C. After stirring for 1 hours, crystals were filtered off and washed with methanol (13L). Methanol-ethanol (1:3, 63 L) was heated to 75° C. and the resultant crystals were added thereto. The mixture was slowly cooled to 25° C. and stirred for 1 hours. Crystals deposited were filtered off and washed with methanol-ethanol (1:1, 13 L). The crystals were dissolved in tetrahydrofuran-water (3:1, 121.4 L) and active carbon (242 g) was added thereto. The mixture was stirred at room temperature for 15 minutes and the active carbon was filtered off. The tetrahydrofuran layer was distilled off under reduced pressure and the resultant aqueous layer was stirred at 25° C. to deposit crystals. The crystals were filtered off to obtain a diastereomer salt of (S)-2-(aminomethyl)-3-chloro-4-(4-methoxyphenyl)-7-oxido-5,8-dihydro-6H-thiopyrano[4′,3′:4,5]thieno[2,3-b]pyridine with (R)-(−)-hydrogenphosphate-1,1′-binaphthyl-2,2′-diyl (4.618 kg, 37.7%). 1H-NMR (DMSO-d6)δ: 1.98–2.04 (1H, m), 2.35–2.43 (1H, m), 2.71–2.81 (1H, m), 3.01–3.06 (1H, m), 3.83 (3H, s), 3.18 (1H, d, J=17.1 Hz), 4.26 (1H, d, J=17.1 Hz), 4.35 (2H, s), 0.07–7.43 (12H, m), 7.96–8.10 (4H, m), 8.64 (3H, bs).

Workup

  1. stirringThe mixture was stirred at 60° C. for 10 minutes
  2. stirringAfter stirring for 1 hours
  3. filtrationcrystals were filtered off
  4. washwashed with methanol (13L)
  5. temperatureMethanol-ethanol (1:3, 63 L) was heated to 75° C.
  6. additionthe resultant crystals were added
  7. temperatureThe mixture was slowly cooled to 25° C.
  8. stirringstirred for 1 hours
  9. filtrationCrystals deposited were filtered off
  10. washwashed with methanol-ethanol (1:1, 13 L)
  11. dissolutionThe crystals were dissolved in tetrahydrofuran-water (3:1, 121.4 L)
  12. additionactive carbon (242 g) was added
  13. stirringThe mixture was stirred at room temperature for 15 minutes
  14. filtrationthe active carbon was filtered off
  15. distillationThe tetrahydrofuran layer was distilled off under reduced pressure
  16. stirringthe resultant aqueous layer was stirred at 25° C.
  17. filtrationThe crystals were filtered off

Sources & evidence

ORD record
ord-bd6b84de9caf47b3955b7b9c154571ca
Source dataset
uspto-grants-2006_06
Patent number
US07067527B2

Reaction notes

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