3-Aminopyridine → HCID 178508459, compound

HRID 1640674Notes

Reaction equation

HRID 1640674 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.C[Al](C)C.[NH2:12][C:13]1[C:14]2[N:15]([C:19]([C@H:31]3[CH2:36][CH2:35][C@H:34]([C:37](OC)=[O:38])[CH2:33][CH2:32]3)=[N:20][C:21]=2[C:22]2[NH:23][C:24]3[C:29]([CH:30]=2)=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH:16]=[CH:17][N:18]=1.[OH-].[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[NH2:12][C:13]1[C:14]2[N:15]([C:19]([C@H:31]3[CH2:32][CH2:33][C@H:34]([C:37]([NH:1][C:2]4[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=4)=[O:38])[CH2:35][CH2:36]3)=[N:20][C:21]=2[C:22]2[NH:23][C:24]3[C:29]([CH:30]=2)=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH:16]=[CH:17][N:18]=1

Participants

7

Reactant 4

HCID 100093-AminopyridineHCID 14798Sodium HydroxideHCID 16682925TrimethylaluminumHCID 178501045HCID 178501045, compound

Product 1

HCID 178508459HCID 178508459, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 3-aminopyridine (40 mg, 0.43 mmol) in toluene (1.3 mL) was treated with a 2M toluene solution of trimethylaluminum (0.3 mL, 0.60 mmol). After 25 min, the resulting solution was treated with methyl trans-4-(8-amino-1-(1H-indol-2-yl)imidazo[1,5-a]pyrazin-3-yl)cyclohexanecarboxylate (30 mg, 0.08 mol) and the mixture stirred at rt overnight. The mixture was then stirred with 2M NaOH (20 mL) and ethyl acetate (20 mL) for 10 min., then the organic phase was separated and the aqueous extracted EtOAc (3×15 mL). The combined organic extracts were washed with water (20 mL) and brine (20 mL), then dried over Na2SO4 and concentrated in vacuo to give crude product which was subjected to mass-directed preparative HPLC to afford pure desired product. 1H NMR (d6-DMSO, 400 MHz): δ 11.45 (br s, 1H), 10.12 (s, 1H), 8.77 (d, J=2.4 Hz, 1H), 8.25 (d, J=4.8 Hz, 1H), 8.14 (s, 1H), 8.08 (dd, J=8.0, 1.6 Hz, 1H), 7.71 (d, J=5.2 Hz, 1H), 7.59 (d, J=7.6 Hz, 1H), 7.46 (d, J=8.4 Hz, 1H), 7.34 (m, 1H), 7.15-7.00 (m, 3H), 6.65 (s, 1H), 6.42 (br s, 2H), 3.22 (m, 1H), 2.47 (m, 1H), 2.15-1.95 (m, 4H), and 1.85-1.65 (m, 4H). MS (ES+): m/z 452.17 [MH+].

Workup

  1. customthe organic phase was separated
  2. extractionthe aqueous extracted EtOAc (3×15 mL)
  3. washThe combined organic extracts were washed with water (20 mL) and brine (20 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customto give crude product which

Sources & evidence

ORD record
ord-24bb36f3eb644b5686ccfe9e92009954
Source dataset
uspto-grants-2012_02
Patent number
US08114846B2

Reaction notes

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