Glyoxylic Acid → [(S)-5-(6-Chloro-9H-beta-carbolin-8-ylcarbamoyl)-2,2-dimethyl-morpholin-4-yl]-acetic acid

HRID 552242

Reaction equation

HRID 552242 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[C:13]([NH:15][C:16]([C@@H:18]3[CH2:23][O:22][C:21]([CH3:25])([CH3:24])[CH2:20][NH:19]3)=[O:17])[CH:14]=1)[NH:11][C:10]1[CH:9]=[N:8][CH:7]=[CH:6][C:5]2=1.C(N(CC)CC)C.C([BH3-])#N.[Na+].[C:37]([OH:41])(=[O:40])[CH:38]=O>CO.O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[C:13]([NH:15][C:16]([C@H:18]3[N:19]([CH2:38][C:37]([OH:41])=[O:40])[CH2:20][C:21]([CH3:25])([CH3:24])[O:22][CH2:23]3)=[O:17])[CH:14]=1)[NH:11][C:10]1[CH:9]=[N:8][CH:7]=[CH:6][C:5]2=1

Participants

7

Reactant 4

HCID 760Glyoxylic AcidHCID 8471TriethylamineHCID 5003444Sodium cyanoborohydrideHCID 67165625(S)-6,6-Dimethyl-morpholine-3-carboxylic acid (6-chloro-9H-beta-carbolin-8-yl)-amide

Product 1

HCID 11384512[(S)-5-(6-Chloro-9H-beta-carbolin-8-ylcarbamoyl)-2,2-dimethyl-morpholin-4-yl]-acetic acidYield 72%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a suspension of (S)-6,6-Dimethyl-morpholine-3-carboxylic acid (6-chloro-9H-beta-carbolin-8-yl)-amide (2.6 g, 6.0 mmoles) in 60 ml of methanol was added 1.7 ml of triethylamine (2.0 eq.), sodium cyanoborohydride (575 mg, 9.1 mmoles) and glyoxylic acid (780 mg, 8.5 mmoles). The reaction mixture was stirred at ambient temperature for 1.5 hrs. Water was added (5 ml) and the mixture was concentrated to a thick yellow slurry. More water was then added (30 ml) and the resulting slurry was stirred at ambient temperature for 10 min. and was filtered. The collected yellow solid was washed with water and dried under high vacuum to give 1.80 g (71%) of the desired product. 1H-NMR (300 MHz, DMSO-d6): δ 1.17 (s,3H), 1.30 (s,3H), 2.81 (d,1H), 3.34 (d,1H), 3.46 (d,1H), 3.56 (dd,1H), 3.84-3.90 (m,2H), 7.92 (s,1H), 8.15 (d,1H), 8.21 (s,1H), 8.36 (d,1H), 9.01 (s,1H), 10.28 (s,1H), 11.40 (s,1H). Retention Time (LC, method: ammonium acetate standard): 1.26 min. MS (M+H+): 417.1.

Workup

  1. concentrationthe mixture was concentrated to a thick yellow slurry
  2. additionMore water was then added (30 ml)
  3. stirringthe resulting slurry was stirred at ambient temperature for 10 min.
  4. filtrationwas filtered
  5. washThe collected yellow solid was washed with water
  6. customdried under high vacuum

Sources & evidence

ORD record
ord-aedccd21893449fe8823a3b0b5a68fd8
Source dataset
uspto-grants-2011_05
Patent number
US07951801B2

Linked notes

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