Trifluoroacetic acid → (R)-2,5-di(1H-indol-4-yl)-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine

HRID 2169648Notes

Reaction equation

HRID 2169648 reaction equation
[NH:1]1[C:9]2[C:4](=[C:5]([C:10]3[N:19]=[CH:18][C:17]4[N:16]([C:20]5[CH:28]=[CH:27][CH:26]=[C:25]6[C:21]=5[CH:22]=[CH:23][N:24]6C(OC(C)(C)C)=O)[CH2:15][C@@H:14]5[CH2:36][O:37][CH2:38][CH2:39][N:13]5[C:12]=4[N:11]=3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[F:40][C:41]([F:46])([F:45])[C:42]([OH:44])=[O:43]>C(Cl)Cl>[C:42]([OH:44])([C:41]([F:46])([F:45])[F:40])=[O:43].[NH:1]1[C:9]2[C:4](=[C:5]([C:10]3[N:19]=[CH:18][C:17]4[N:16]([C:20]5[CH:28]=[CH:27][CH:26]=[C:25]6[C:21]=5[CH:22]=[CH:23][NH:24]6)[CH2:15][C@@H:14]5[CH2:36][O:37][CH2:38][CH2:39][N:13]5[C:12]=4[N:11]=3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68195017(R)-tert-butyl 4-(2-(1H-indol-4-yl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)-1H-indole-1-carboxylate

Product 2

HCID 6422Trifluoroacetic acidHCID 68194900(R)-2,5-di(1H-indol-4-yl)-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridineYield 28%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(R)-tert-Butyl 4-(2-(1H-indol-4-yl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)-1H-indole-1-carboxylate (PREPARATION x65, 9 mg, 0.017 mmol) was dissolved in CH2Cl2 (1 mL) and trifluoroacetic acid (1 mL) and the mixture was stirred at room temperature for 30 minutes. The material was then concentrated in vacuo and the product was purified by LC/MS using a 20-45% CH3CN gradient in H2O (with 0.035% TFA). The pure fractions were combined and lyophilized to afford a TFA salt of the title compound as a yellow solid (2 mg, 28%). 1H NMR (400 MHz, CD3CN) δ ppm 3.36-3.61 (m, 3 H), 3.68-3.87 (m, 2 H), 3.97-4.07 (m, 1 H), 4.07-4.20 (m, 2 H), 4.91-5.00 (m, 1 H), 6.28-6.38 (m, 1 H), 6.98-7.09 (m, 2 H), 7.12-7.17 (m, 1 H), 7.22-7.35 (m, 3 H), 7.44-7.51 (m, 2 H), 7.65-7.75 (m, 2 H), 9.57-9.67 (m, 1 H), 9.67-9.81 (m, 1 H); ESI-MS m/z [M+H]+ calc'd for C25H22N6O, 423.19; found 423.3.

Workup

  1. concentrationThe material was then concentrated in vacuo
  2. customthe product was purified by LC/MS

Sources & evidence

ORD record
ord-f07b4cb4d0874d16aea38358b123f29f
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

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