Diisopropylethylamine → HCID 57512640, compound

HRID 971330Notes

Reaction equation

HRID 971330 reaction equation
[CH3:1][S:2]([NH:5][C:6]1[O:7][CH:8]=[C:9]([C:11]([OH:13])=O)[N:10]=1)(=[O:4])=[O:3].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.Cl.Cl.[NH2:49][C@@H:50]([CH2:64][C:65]1[CH:70]=[CH:69][CH:68]=[C:67]([O:71][CH2:72][CH2:73][CH2:74][CH3:75])[CH:66]=1)[C@H:51]([OH:63])[CH2:52][NH:53][CH2:54][C:55]1[CH:60]=[CH:59][CH:58]=[C:57]([CH2:61][CH3:62])[CH:56]=1>C(Cl)Cl>[CH2:72]([O:71][C:67]1[CH:66]=[C:65]([CH:70]=[CH:69][CH:68]=1)[CH2:64][C@H:50]([NH:49][C:11]([C:9]1[N:10]=[C:6]([NH:5][S:2]([CH3:1])(=[O:3])=[O:4])[O:7][CH:8]=1)=[O:13])[C@H:51]([OH:63])[CH2:52][NH:53][CH2:54][C:55]1[CH:60]=[CH:59][CH:58]=[C:57]([CH2:61][CH3:62])[CH:56]=1)[CH2:73][CH2:74][CH3:75]

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11401481HCID 11401481, compoundHCID 69318676HCID 69318676, compound

Product 1

HCID 57512640HCID 57512640, compoundYield 6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxylic acid (43) (100 mg, 0.5 mmol) and HATU (180 mg, 0.5 mmol) in methylene chloride (3 mL) was added N,N-diisopropylethylamine (100 μL, 0.6 mmol). In a separate flask, N,N-diisopropylethylamine (200 μL, 1.2 mmol) was added to amine 48 (135 mg, 0.3 mmol) in methylene chloride (2 mL). This solution was added to the above solution containing the acid and the resulting reaction mixture was stirred at room temperature for 18 h. The reaction mixture was partitioned between methylene chloride and water. The organic layer was washed with water, dried (sodium sulfate), filtered, and concentrated under reduced pressure to afford a crude oil. Purification by flash column chromatography (silica, gradient 93:7 to 90:10 methylene chloride/methanol) provided N-{(1S,2R)-1-(3-butoxybenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-2-[(methylsulfonyl)amino]-1,3-oxazole-4-carboxamide (50a) (10 mg): mp 78–80° C.; IR (KBr) 2960, 1602, 1581, 1490, 1450 cm−1; 1H NMR (500 MHz, CD3OD) δ 7.67 (s, 1H), 7.34–7.09 (m, 5H), 6.82–6.68 (m, 3H), 4.18 (s, 2H), 4.07–4.05 (m, 1H), 3.90–3.84 (m, 3H), 3.23–3.16 (m, 2H), 3.04 (s, 3H), 3.04–3.01 (m, 1H), 2.75–2.64 (m, 3H), 1.69–1.66 (m, 2H), 1.46–1.42 (m, 2H), 1.21 (t, J=8 Hz, 3H), 0.94 (t, J=8 Hz, 3H); ESI-MS m/z 559 [M+H]+.

Workup

  1. additionThis solution was added to the above solution
  2. additioncontaining the acid
  3. customthe resulting reaction mixture
  4. customThe reaction mixture was partitioned between methylene chloride and water
  5. washThe organic layer was washed with water
  6. dry with materialdried (sodium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto afford a crude oil
  10. customPurification by flash column chromatography (silica, gradient 93:7 to 90:10 methylene chloride/methanol)

Sources & evidence

ORD record
ord-396ed852963f446a9659784846adcacb
Source dataset
uspto-grants-2007_12
Patent number
US07312360B2

Reaction notes

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