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Formate → (R)-propyl 2-(7-amino-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl)acetate

HRID 475488
ノート
印刷プレビュー

反応式

HRID 475488 の反応式
P([O-])([O-])([O-])=O.[Na+].[Na+].[Na+].[CH:9]([O-:11])=[O:10].[Na+].[NH2:13][C@@H:14]([C:16](O)=O)[CH3:15].C1C=[N+:23]([C@@H:25]2O[C@H:28]([CH2:30]OP(OP(OC[C@H]3O[C@@H](N4C5N=CN=C(N)C=5N=C4)[C@H](O)[C@@H]3O)(O)=O)([O-])=O)[C@@H:27](O)[C@H:26]2O)[CH:22]=[C:21]([C:60](N)=O)[CH:20]=1.[CH3:63][C:64]1[C:69](O)=C(C=O)C(COP(O)(O)=O)=CN=1.[C:79]([O-])(=O)C(C)O.C([O-])=O.Cl>O>[NH2:13][C@H:14]1[CH2:16][N:23]2[C:25]3[C:60]([C:21]([CH2:20][C:9]([O:11][CH2:63][CH2:64][CH3:69])=[O:10])=[C:22]2[CH2:79][CH2:15]1)=[CH:30][CH:28]=[CH:27][CH:26]=3
参加物実験手順後処理出典と根拠反応ノート

参加物

10

反応物 8

HCID 283FormateHCID 313Hydrochloric AcidHCID 1051Pyridoxal 5'-phosphateHCID 5892NadideHCID 24243Trisodium PhosphateHCID 71080D-AlanineHCID 91435Lactate
HCID 2723810
Sodium Formate

生成物 1

HCID 58349691(R)-propyl 2-(7-amino-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl)acetate収率 80%

試薬・触媒・溶媒 1

HCID 962Water溶媒

実験手順

Sodium phosphate, dibasic (3.8 equiv.) and sodium formate (266 equiv.) were added to a solution of D-Alanine (38 equiv.) in water. The pH was measured as 7.6. Nicotinamide Adenine Dinucleotide (0.04 equiv.), Pyridoxal-5-phosphate (0.11 equiv.), Lactate dehydrogenase (1 equiv.), Formate dehydrogenase (1 equiv.), and Amine-Transaminase-117 (1 equiv.) were added under stirring and slowly dissolved. The measured pH was 7.3. The mixture was aged at 22° C. for 1 h. The flask was flushed with nitrogen and propyl (7-oxo-6,7,8,9-tetrahydropyrido[1,2-α]indol-10-yl)acetate from Step 5 was added as a DMSO (0.06 M) solution. The reaction was adjusted to pH 7.2 and aged at 30° C. overnight under nitrogen atmosphere. Upon completion of the reaction as determined by HPLC, the pH of the reaction was adjusted to pH 4.0 with 6 N HCl and Celite (20 g per L) was added. After stirring for 1 hr the reaction was filtered through a Celite bed and the filter cake was washed twice with 0.1 N HCl. The combined aqueous filtrate was extracted with 1 volume of MTBE. The organic layer did not contain amine and was discarded. The aqueous layer was diluted with an equal volume of MTBE and the pH of the mixture was adjusted to pH 9.5 using 5N NaOH. The two phases were separated and the aqueous layer was extracted with MTBE. The spent aqueous layer had no detectable amine and was discarded. The combined organic layers were washed with dilute sodium carbonate and dried over Na2SO4. Evaporation of the volatiles afforded the crude title compound (80%). The ee was determined as 99% by SFC assay. The SFC conditions are ADH column (250×4.6 mm, 5 um), isocratic 20% MeOH, 25 mM iso-proply amine/CO2, 2 ml/min, 35° C., 200 bar, 215 nm, 15 min. Under these conditions the desired R-amine has an 8.99 min retention time (S-amine; 5.82 min)

後処理

  1. dissolutionslowly dissolved
  2. customThe flask was flushed with nitrogen and propyl (7-oxo-6,7,8,9-tetrahydropyrido[1,2-α]indol-10-yl)acetate from Step 5
  3. additionwas added as a DMSO (0.06 M) solution
  4. waitaged at 30° C. overnight under nitrogen atmosphere
  5. customUpon completion of the reaction
  6. additionwas added
  7. stirringAfter stirring for 1 hr the reaction
  8. filtrationwas filtered through a Celite bed
  9. washthe filter cake was washed twice with 0.1 N HCl
  10. extractionThe combined aqueous filtrate was extracted with 1 volume of MTBE
  11. additionThe aqueous layer was diluted with an equal volume of MTBE
  12. customThe two phases were separated
  13. extractionthe aqueous layer was extracted with MTBE
  14. washThe combined organic layers were washed with dilute sodium carbonate
  15. dry with materialdried over Na2SO4
  16. customEvaporation of the volatiles

出典と根拠

ORDレコード
ord-97054c43b03f45369be7288ca0117c46
出典データセット
uspto-grants-2014_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08637541B2

反応ノート

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