Cyclopropylamine → HCID 178461876, compound

HRID 75900Notes

Reaction equation

HRID 75900 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.[CH:29]1([NH2:32])[CH2:31][CH2:30]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[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](/[CH:14]=[N:32]/[CH:29]4[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 69828CyclopropylamineHCID 5049666Sodium triacetoxyborohydrideHCID 86620610(S)-6-(5-Cyclopropyl-1H-pyrazol-3-ylamino)-5-fluoro-2-(1-(4-fluorophenyl)ethylamino)nicotinaldehyde

Product 1

HCID 178461876HCID 178461876, compoundYield 62%

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 cyclopropanamine (0.03 g, 0.52 mmol) and NaBH(OAc)3 (0.55 g, 0.26 mmol). The reaction was stirred for 3 hours, quenched with aqueous 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 (0.068 g, 62%). 1H NMR (400 MHz) δ 11.92 (s, 1H), 9.62 (s, 1H), 8.93 (s, 1H), 8.35 (s, 1H), 7.39 (d, J=7.4 Hz, 1H), 7.31-7.27 (m, 2H), 7.16-7.11 (m, 2H), 6.10 (s, 1H), 5.13-5.10 (m, 1H), 2.96-2.94 (m, 1H), 1.89-1.80 (m, 1H), 1.42 (d, J=6.9 Hz, 3H), 0.98-0.88 (m, 2H), 0.76-0.63 (m, 2H). MS: Calcd.: 422. Found: [M+H]+ 423.

Workup

  1. customquenched with aqueous 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-c2567b6f28e54e70be5551e633669f51
Source dataset
uspto-grants-2014_09
Patent number
US08835465B2

Reaction notes

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