Butanoic acid, 4-chloro-4-oxo-, methyl ester → Methyl 4-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenylamino)-4-oxobutanoate

HRID 1177634

Reaction equation

HRID 1177634 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH2:26])[CH:5]=[CH:6][C:7]=1[C:8]1[S:9][C:10]2[C:15]([N:16]=1)=[CH:14][CH:13]=[C:12]([C:17]1([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:19][CH2:18]1)[N:11]=2.C(N(C(C)C)C(C)C)C.Cl[C:37](=[O:44])[CH2:38][CH2:39][C:40]([O:42][CH3:43])=[O:41]>C1COCC1.C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([NH:26][C:37](=[O:44])[CH2:38][CH2:39][C:40]([O:42][CH3:43])=[O:41])[CH:5]=[CH:6][C:7]=1[C:8]1[S:9][C:10]2[C:15]([N:16]=1)=[CH:14][CH:13]=[C:12]([C:17]1([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH2:18][CH2:19]1)[N:11]=2

Participants

6

Reactant 3

HCID 73888Butanoic acid, 4-chloro-4-oxo-, methyl esterHCID 81531DiisopropylethylamineHCID 574030523-Fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)benzenamine

Product 1

HCID 67111772Methyl 4-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenylamino)-4-oxobutanoate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

3-Fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)benzenamine (140 mg, 0.387 mmol) was dissolved in THF (3.9 mL) and N-ethyl-N-isopropylpropan-2-amine (270 μl, 1.55 mmol) before methyl 4-chloro-4-oxobutanoate (189 μl, 1.55 mmol) was added at ambient temperature and the reaction mixture was stirred at ambient temperature for 30 min. The reaction mixture was diluted with 100 mL of DCM, added to a separatory funnel, partitioned with water, washed 2 times with 50 mL of sodium bicarbonate (saturated, aqueous), separated, dried over sodium sulfate, and concentrated via rotovap to give methyl 4-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenylamino)-4-oxobutanoate after flash chromatography. MS (ESI) m/z: Calculated: 475.1; Observed: 476.4 (M++1).

Workup

  1. additionadded to a separatory funnel
  2. custompartitioned with water
  3. washwashed 2 times with 50 mL of sodium bicarbonate (saturated, aqueous)
  4. customseparated
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated via rotovap

Sources & evidence

ORD record
ord-195398b5271f421c8d816273a66dd89a
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Linked notes

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