6-Fluoropyridin-2-amine → HCID 68688006, compound

HRID 1157798Notes

Reaction equation

HRID 1157798 reaction equation
NC1C=CC=C(F)N=1.[F:9][C:10]1[N:15]=[C:14]([N:16]2[C:20]([N:21]3[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]3)=[N:19][N:18]=[N:17]2)[CH:13]=[CH:12][CH:11]=1.[N:34]([C:37]1[N:42]=[C:41]([N:43]2[C:47]([N:48]3[CH2:53][CH2:52][N:51]([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH2:50][CH2:49]3)=[N:46][N:45]=[N:44]2)[CH:40]=[CH:39][CH:38]=1)=[N+]=[N-].[BH4-].[Na+]>CO.O>[F:9][C:10]1[N:15]=[C:14]([N:16]2[C:20]([N:21]3[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]3)=[N:19][N:18]=[N:17]2)[CH:13]=[CH:12][CH:11]=1.[NH2:34][C:37]1[N:42]=[C:41]([N:43]2[C:47]([N:48]3[CH2:53][CH2:52][N:51]([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH2:50][CH2:49]3)=[N:46][N:45]=[N:44]2)[CH:40]=[CH:39][CH:38]=1

Participants

8

Reactant 4

HCID 27613996-Fluoropyridin-2-amineHCID 4311764Sodium borohydrideHCID 68688006HCID 68688006, compoundHCID 86620658HCID 86620658, compound

Product 2

HCID 68688006HCID 68688006, compoundHCID 68693005HCID 68693005, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
25 °C

Procedure

Part C′: When the procedures described above were employed utilizing 2-amino-6-fluoropyridine as the commercial starting material the isolated crude product of part C was 3.90 g of a mixture of tert-butyl 4-(1-(6-fluoropyridin-2-yl)-1H-tetrazol-5-yl)piperazine-1-carboxylate and tert-butyl 4-(1-(6-azidopyridin-2-yl)-1H-tetrazol-5-yl)piperazine-1-carboxylate. This crude product was dissolved in a mixture of 120 mL of methanol and 20 mL of water. To this solution at 25° C. was added in portions 1.60 g of sodium borohydride, and the mixture was stirred at 25° C. for 4 h. The reaction mixture then was concentrated under vacuum, and the residue was diluted with water and ethyl acetate. The phases were separated, and the organic phase was washed with water (×2) and brine, dried over anhydrous sodium sulfate, filtered, and concentrated. Column chromatography on silica gel (elution: 0-100% diethyl ether/methylene chloride) afforded tert-butyl 4-(1-(6-fluoropyridin-2-yl)-1H-tetrazol-5-yl)piperazine-1-carboxylate (3.26 g) [Mass Spec.: m/e: 350.32 (M+H)+ [calc'd: 350.17]; 1H NMR (300 MHz, CDCl3) δ 8.05 (m, 1H), 7.78 (m, 1H), 7.05 (m, 1H), 3.60 (m, 4H), 3.40 (m, 4H), 1.46 (s, 9H)] and tert-butyl 4-(1-(6-aminopyridin-2-yl)-1H-tetrazol-5-yl)piperazine-1-carboxylate (0.28 g) [Mass Spec.: m/e: 347.37 (M+H)+ [calc'd: 347.19]; 1H NMR (300 MHz, DMSO-D6) δ 7.64 (t, 1H, J=8 Hz), 6.79 (d, 1H, J=8 Hz), 6.60 (d, 1H, J=8 Hz), 6.55 (br s, 2H), 3.40 (m, 4H), 3.24 (m, 4H), 1.41 (s, 9H)].

Workup

  1. customisolated crude product of part C
  2. concentrationThe reaction mixture then was concentrated under vacuum
  3. additionthe residue was diluted with water and ethyl acetate
  4. customThe phases were separated
  5. washthe organic phase was washed with water (×2) and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-d26df697f2fc4573adaa46b90979d8fb
Source dataset
uspto-grants-2010_10
Patent number
US07807676B2

Reaction notes

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