Azide → HCID 11306629, compound

HRID 1987167Notes

Reaction equation

HRID 1987167 reaction equation
[N-]=[N+]=[N-].[N:4]([C@@H:7]([CH2:37][CH2:38][CH2:39][CH3:40])[C@@H:8]([NH:16][C:17](=[O:36])[C:18]1[CH:23]=[C:22]([N:24]([CH3:29])[S:25]([CH3:28])(=[O:27])=[O:26])[N:21]=[C:20]([NH:30][CH2:31][CH:32]2[CH2:34][CH:33]2[CH3:35])[CH:19]=1)[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[N+]=[N-]>CO.[Pd]>[NH2:4][C@@H:7]([CH2:37][CH2:38][CH2:39][CH3:40])[C@@H:8]([NH:16][C:17](=[O:36])[C:18]1[CH:23]=[C:22]([N:24]([CH3:29])[S:25]([CH3:28])(=[O:27])=[O:26])[N:21]=[C:20]([NH:30][CH2:31][CH:32]2[CH2:34][CH:33]2[CH3:35])[CH:19]=1)[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

5

Reactant 2

HCID 33558AzideHCID 86613213HCID 86613213, compound

Product 1

HCID 11306629HCID 11306629, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent2×

Procedure

Amide Formation A solution of acid intermediate A (35 mg, 0.112 mmol), amine intermediate I (28 mg, 0.134 mmol), N,N-diisopropylethylamine (36 mg, 0.28 mmol), and HOAT (15 mg, 0.112 mmol) in methylene chloride (1.5 mL) was treated with EDC (32 mg, 0.168 mmol). After stirring 2 hours at ambient temperature the solution was partitioned between water/methylene chloride. The organics were washed with 1N HCl followed by brine. The combined organics were dried over sodium sulfate, filtered and evaporated in vacuo to give N-[(1S,2S)-2-azido-1-benzylhexyl]-2-{[(2-methylcyclopropyl)methyl]amino}-6-[methyl(methylsulfonyl)amino]isonicotinamide as a crude oil. LCMS (M+H)=528.0 Step B: Azide Reduction A solution of crude N-[(1S,2S)-2-azido-1-benzylhexyl]-2-{[(2-methylcyclopropyl)methyl]amino}-6-[methyl(methylsulfonyl)amino]isonicotinamide in methanol (2 mL) and 10% palladium on carbon (12 mg) in degassed methanol was placed under a hydrogen atmosphere for 1 hour. The reaction was filtered through celite, rinsed with methanol and evaporated in vacuo. Purification by reverse phase LC gave N-[(1S,2S)-2-amino-1-benzylhexyl]-2-{[(2-methylcyclopropyl)methyl]amino}-6-[methyl(methylsulfonyl)amino]isonicotinamide. 1H NMR (CD3OD) δ 7.28 (m, 5H), 6.55 (s, 1H), 6.44 (s, 1H), 4.35 (m, 1H), 3.42 (m, 1H), 3.29 (s, 3H), 3.16 (m, 5H), 3.00 (m, 2H), 1.85 (m, 1H), 1.72 (m, 1H), 1.43 (m, 4H), 1.05 (d, J=5.96 Hz, 3H), 0.98 (t, J=7.14 Hz, 3H), 0.80 (m, 1H), 0.65 (m, 1H), 0.41 (m, 1H), 0.24 (m, 1H) LCMS [M+H]+=314.1. The following examples were prepared in an analogous manner to that described in Example 1 using various combinations of Intermediates I-XXX or related derivatives thereof and Intermediate acids of types A-H or related derivatives thereof.

Workup

  1. filtrationThe reaction was filtered through celite
  2. washrinsed with methanol
  3. customevaporated in vacuo
  4. customPurification by reverse phase LC

Sources & evidence

ORD record
ord-e3ec30ad1c0041d2b12c89a881fcfeb7
Source dataset
uspto-grants-2009_06
Patent number
US07550481B2

Reaction notes

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