Diisopropylethylamine → HCID 178475041, compound

HRID 2246583Notes

Reaction equation

HRID 2246583 reaction equation
[NH2:1][C@H:2]1[CH2:6][CH2:5][N:4]([C@H:7]2[CH2:12][CH2:11][C@@H:10]([N:13]([CH:15]([CH3:17])[CH3:16])[CH3:14])[CH2:9][C@H:8]2[NH:18][C:19](=[O:21])[CH3:20])[C:3]1=[O:22].O([C:30]1[C:39]2[C:34](=[CH:35][CH:36]=[C:37]([C:40]([F:43])([F:42])[F:41])[CH:38]=2)[N+:33]([O-:44])=[CH:32][N:31]=1)C1C=CC=CC=1.C(N(CC)C(C)C)(C)C>CC(O)C>[C:19]([NH:18][C@@H:8]1[CH2:9][C@H:10]([N:13]([CH:15]([CH3:17])[CH3:16])[CH3:14])[CH2:11][CH2:12][C@@H:7]1[N:4]1[CH2:5][CH2:6][C@H:2]([NH:1][C:30]2[C:39]3[C:34](=[CH:35][CH:36]=[C:37]([C:40]([F:43])([F:41])[F:42])[CH:38]=3)[N+:33]([O-:44])=[CH:32][N:31]=2)[C:3]1=[O:22])(=[O:21])[CH3:20]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 44185161N-((1R,2S,5R)-2-((S)-3-amino-2-oxopyrrolidin-1-yl)-5-(isopropyl(methyl)amino)cyclohexyl)acetamideHCID 685663764-Phenoxy-6-(trifluoromethyl)quinazoline 1-oxide

Product 1

HCID 178475041HCID 178475041, compoundYield 110.5%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
120 °C

Procedure

Example 5, Alternative Preparation, Step 3: To a solution of N-((1R,2S,5R)-2-((S)-3-amino-2-oxopyrrolidin-1-yl)-5-(isopropyl(methyl)amino)cyclohexyl)acetamide (50 mg, 0.161 mmol; see Example 1, Step 10) and 4-phenoxy-6-(trifluoromethyl)quinazoline 1-oxide (99 mg, 0.161 mmol) in i-PrOH (2 ml) was added N,N-diisopropylethylamine (0.056 ml, 0.322 mmol). The vessel was sealed under argon and heated in a microwave for 1 hr at 120° C. LC/MS found: (M+H)+=523.3 as the major product peak. The mixture was concentrated and purified by automated flash chromatography (40 g silica gel, eluting with 8:92 10% cNH4OH/MeOH). The fractions containing the desired product were pooled and concentrated in vacuo. The residue was crystallized from CH2Cl2 and hexane. The two crops were combined and dried under vacuum to afford the title compound, 4-((S)-1-((1S,2R,4R)-2-acetamido-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-ylamino)-6-(trifluoromethyl)quinazoline 1-oxide (93 mg). Analysis by 1H-NMR showed that this material contained ˜0.75 molar equivalents of CH2Cl2. 1H-NMR (400 MHz, d4-MeOH): δ 8.99 (s, 1H), 8.81 (s, 1H), 8.62 (d, J=8.9 Hz, 1H), 8.32 (dd, J=9.0, 1.5 Hz, 1H), 5.28 (t, J=8.4 Hz, 1H), 4.59 (br s, 1H), 4.05 (m, 1H), 3.55-3.65 (m, 2H), 3.43 (m, 1H), 2.75 (br s, 1H), 2.55 (m, 1H), 2.27 (s, 3H), 2.1-2.3 (m, 3H), 2.02 (s, 3H), 2.0 (m, 1H), 1.65-1.7 (m, 3H), 1.12 (d, J=6.0 Hz, 3H), 1.06 (d, J=6.0 Hz, 3H). LC/MS found: [M+H]+=523.33.

Workup

  1. customExample 5, Alternative Preparation, Step 3
  2. customThe vessel was sealed under argon
  3. concentrationThe mixture was concentrated
  4. custompurified by automated flash chromatography (40 g silica gel, eluting with 8:92 10% cNH4OH/MeOH)
  5. additionThe fractions containing the desired product
  6. concentrationconcentrated in vacuo
  7. customThe residue was crystallized from CH2Cl2 and hexane
  8. customdried under vacuum

Sources & evidence

ORD record
ord-6f990ef72e5e40c383fd1deaa08c2bc7
Source dataset
uspto-grants-2010_03
Patent number
US07687508B2

Reaction notes

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