Diisopropylethylamine → HCID 136121462, compound

HRID 2062339Notes

Reaction equation

HRID 2062339 reaction equation
C(N(C(C)C)C(C)C)C.[NH2:10][C@@H:11]1[CH2:15][CH2:14][N:13]([C:16]2[C:25]3[C:20](=[CH:21][C:22]([CH3:26])=[CH:23][CH:24]=3)[N:19]=[C:18]([C:27]3[C:32]([F:33])=[CH:31][CH:30]=[CH:29][C:28]=3[OH:34])[N:17]=2)[CH2:12]1.Cl[C:36]([O:38][C@H:39]1[CH2:43][CH2:42][O:41][CH2:40]1)=[O:37]>C1COCC1>[F:33][C:32]1[CH:31]=[CH:30][CH:29]=[C:28]([OH:34])[C:27]=1[C:18]1[N:17]=[C:16]([N:13]2[CH2:14][CH2:15][C@@H:11]([NH:10][C:36](=[O:37])[O:38][C@H:39]3[CH2:43][CH2:42][O:41][CH2:40]3)[CH2:12]2)[C:25]2[C:20](=[CH:21][C:22]([CH3:26])=[CH:23][CH:24]=2)[N:19]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 22876378(3S)-oxolan-3-yl carbonochloridateHCID 136121403HCID 136121403, compound

Product 1

HCID 136121462HCID 136121462, compoundYield 88.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

At room temperature, N-ethyl-N-isopropylpropan-2-amine (155 mL, 0.88 mmol) was added to a solution of 2-(4-((R)-3-aminopyrrolidin-1-yl)-7-methylquinazolin-2-yl)-3-fluorophenol (150 mg, 0.40 mmol) in THF. The mixture was cooled in an ice bath, and (S)-tetrahydrofuran-3-yl chloroformate (63 mg, 0.42 mmol) was added slowly over a period of 10 minutes. After warming to room temperature, the reaction was quenched with water and extracted twice with CH2Cl2. The combined organic layers were dried over MgSO4, filtered, and concentrated. Purification via silica gel chromatography using 0-10% EtOAc in CH2Cl2/hexanes (1:1) gave (S)-tetrahydrofuran-3-yl(R)-1-(2-(2-fluoro-6-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamate (160 mg, 84%). LC/MS: m/z 453.3 (M+H)+ at 2.12 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)). 1H NMR (400 MHz, DMSOd6) δ 8.18 (d, J=8.6 Hz, 1H), 7.70 (d, J=6.3 Hz, 1H), 7.58 (s, 1H), 7.29-7.38 (m, 2H), 6.76 (d, J=8.3 Hz, 1H), 6.67-6.72 (m, 1H), 5.14 (s, 1H), 4.23-4.24 (m, 1H), 3.99-4.13 (m, 3H), 3.64-3.85 (m, 5H), 2.50 (s, 3H), 2.07-2.22 (m, 2H), 2.00-2.03 (m, 1H), 1.85-1.90 (m, 1H).

Workup

  1. temperatureThe mixture was cooled in an ice bath
  2. customthe reaction was quenched with water
  3. extractionextracted twice with CH2Cl2
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification via silica gel chromatography

Sources & evidence

ORD record
ord-d6d7066687de4cee93c6555c6c2a536a
Source dataset
uspto-grants-2012_10
Patent number
US08283354B2

Reaction notes

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