Morpholine → HCID 69286265, compound

HRID 2189857Notes

Reaction equation

HRID 2189857 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.[NH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl>[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][N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)=[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

5

Reactant 3

HCID 8083MorpholineHCID 5049666Sodium triacetoxyborohydrideHCID 86620610(S)-6-(5-Cyclopropyl-1H-pyrazol-3-ylamino)-5-fluoro-2-(1-(4-fluorophenyl)ethylamino)nicotinaldehyde

Product 1

HCID 69286265HCID 69286265, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of (S)-6-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-fluoro-2-(1-(4-fluorophenyl)ethylamino)nicotinaldehyde (Example 73, 0.12 g, 0.31 mmol) in DCE (5 ml) was added morpholine (0.1 g, 1.14 mmol) and NaBH(OAc)3 (0.30 g, 1.5 mmol). The reaction was then stirred for 2 days, 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 (0.09 g, 67%). 1H NMR (400 MHz, CD3OD) δ 7.41 (br s, 2H), 7.06-7.02 (m, 3H), 6.13 & 5.44 (s, 1H), 5.12 & 4.97 (s, 1H), 3.63 (br s, 4H), 3.42 (br s, 2H), 2.41 (br s, 4H), 1.87-1.82 (m, 1H), 1.54 (d, J=6.5 Hz, 3H), 0.96-0.90 (m, 2H), 0.65-0.64 (m, 2H). MS: Calcd.: 454. Found: [M+H]+ 455.

Workup

  1. customquenched with aq. Na2CO3 (10 ml)
  2. extractionextracted with DCM (2×20 ml)
  3. dry with materialThe combined organic fractions were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting oil was purified by reverse-phase column chromatography (5-35% ACN)

Sources & evidence

ORD record
ord-d45287ea2c0f4860a38213911e6f50d2
Source dataset
uspto-grants-2012_12
Patent number
US08324252B2

Reaction notes

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