Methylamine → HCID 69286786, compound

HRID 75902Notes

Reaction equation

HRID 75902 reaction equation
[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[C:17]([F:18])=[CH:16][C:13]([CH:14]=O)=[C:12]([NH:19][C@H:20]([C:22]4[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=4)[CH3:21])[N:11]=3)[CH:5]=2)[CH2:3][CH2:2]1.[CH3:29][NH2:30].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[BH4-].[Na+]>C1COCC1>[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[C:17]([F:18])=[CH:16][C:13]([CH2:14][NH:30][CH3:29])=[C:12]([NH:19][C@H:20]([C:22]4[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=4)[CH3:21])[N:11]=3)[CH:5]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 6329MethylamineHCID 4311764Sodium borohydrideHCID 5049666Sodium triacetoxyborohydrideHCID 86620610(S)-6-(5-Cyclopropyl-1H-pyrazol-3-ylamino)-5-fluoro-2-(1-(4-fluorophenyl)ethylamino)nicotinaldehyde

Product 1

HCID 69286786HCID 69286786, compoundYield 48.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-6-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-fluoro-2-(1-(4-fluorophenyl)ethylamino)nicotinaldehyde (Example 73, 0.10 g, 0.26 mmol) in THF (5 ml) was added methylamine (2.0 M in THF, 0.52 mmol) and NaBH(OAc)3 (0.82 g, 0.39 mmol). The reaction was stirred for 3 hours, quenched with water, and extracted with DCM (2×20 ml). The combined organic fractions were dried over Na2SO4, filtered, and then concentrated. The resulting crude imine was dissolved in MeOH (5 ml) and NaBH4 (0.06 g, 0.4 mmol) was added. The reaction was stirred for 10 min, quenched with aq. Na2CO3 (10 ml), and extracted with DCM (2×20 ml). The combined organic fractions were dried over Na2SO4, filtered, and then concentrated. The resulting oil was purified by reverse phase column chromatography (5-35% ACN) to give the title compound (0.05 g, 48%). 1H NMR (400 MHz, CD3OD) δ 7.41-7.38 (m, 2H), 7.10 (d, J=9.2 Hz, 1H), 7.02-6.98 (m, 2H), 6.00-5.52 (br s, 1H), 5.05 (s, 1H), 3.63 (s, 2H), 2.37 (s, 3H), 1.87-1.82 (m, 1H), 1.51 (d, J=6.9 Hz, 3H), 0.93-0.91 (m, 2H), 0.67-0.63 (m, 2H). MS: Calcd.: 398. Found: [M+H]+399.

Workup

  1. customquenched with water
  2. extractionextracted with DCM (2×20 ml)
  3. dry with materialThe combined organic fractions were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe resulting crude imine was dissolved in MeOH (5 ml)
  7. stirringThe reaction was stirred for 10 min
  8. customquenched with aq. Na2CO3 (10 ml)
  9. extractionextracted with DCM (2×20 ml)
  10. dry with materialThe combined organic fractions were dried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe resulting oil was purified by reverse phase column chromatography (5-35% ACN)

Sources & evidence

ORD record
ord-cc60204040ba40548fe0a494f087bf50
Source dataset
uspto-grants-2014_09
Patent number
US08835465B2

Reaction notes

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