Water → 3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-thiophene-2-carboxylic acid [2-(3-fluorophenyl)-ethyl]-amide

HRID 570497Notes

Reaction equation

HRID 570497 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[CH2:5][CH2:6][NH2:7].C[Al](C)C.C(N[C:23]([C:25]1[S:26][CH:27]=[CH:28][C:29]=1[NH:30][C:31]1[C:32]2[CH:39]=[CH:38][NH:37][C:33]=2[N:34]=[CH:35][N:36]=1)=[O:24])C1C=CC=CC=1.O>C1(C)C=CC=CC=1.CO>[F:1][C:2]1[CH:3]=[C:4]([CH2:5][CH2:6][NH:7][C:23]([C:25]2[S:26][CH:27]=[CH:28][C:29]=2[NH:30][C:31]2[C:32]3[CH:39]=[CH:38][NH:37][C:33]=3[N:34]=[CH:35][N:36]=2)=[O:24])[CH:8]=[CH:9][CH:10]=1

Participants

7

Reactant 4

HCID 962WaterHCID 5339282-(3-Fluorophenyl)ethanamineHCID 16682925TrimethylaluminumHCID 509238613-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-thiophene-2-carboxylic acid benzylamide

Product 1

HCID 509237253-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-thiophene-2-carboxylic acid [2-(3-fluorophenyl)-ethyl]-amideYield 12.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent2×

Procedure

To a solution of 3-fluorophenethylamine (130 μL; 134 mg; 0.97 mmol) in anhydrous toluene (3 mL) placed in a microwave tube under nitrogen was added a solution of trimethylaluminum (390 μL; 2.00 M; 0.77 mmol) in toluene. The colorless solution was stirred at 25° C. for 15 min, before 3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-thiophene-2-carboxylic acid benzylamide (60 mg; 0.19 mmol), was added. The resulting green solution was stirred for 15 min under a flow of nitrogen, and microwaved to 120° C. for 30 min. The reaction mixture was allowed to cool down before water (0.1 mL) was added. The resulting beige suspension was stirred at 25° C. for 2 h, diluted with methanol and purified by chromatography on a SP1 Biotage system, using dichloromethane and methanol as eluents to afford 3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-thiophene-2-carboxylic acid [2-(3-fluorophenyl)-ethyl]-amide (9 mg, 12%) as a white solid (HPLC: 98%, RT: 6.33 min). 1H NMR (DMSO-d6) 11.97 (br s, 1H), 11.37 (s, 1H), 8.48 (d, J=5.5 Hz, 1H), 8.38 (s, 1H), 8.33 (t, J=5.5 Hz, 1H), 7.75 (d, J=5.5 Hz, 1H), 7.37 (dd, J=3.7, 2.6 Hz, 1H), 7.33 (t, J=7.7 Hz, 1H), 7.13-7.08 (m, 2H), 7.03 (td, J=8.1, 2.6 Hz, 1H), 6.45 (dd, J=3.7, 1.8 Hz, 1H), 3.53 (q, J=6.6 Hz, 2H), 2.90 (t, J=7.1 Hz, 2H); MS (m/z) 382 [M+H]+.

Workup

  1. additionwas added
  2. custommicrowaved to 120° C. for 30 min
  3. additionwas added
  4. stirringThe resulting beige suspension was stirred at 25° C. for 2 h
  5. custompurified by chromatography on a SP1 Biotage system

Sources & evidence

ORD record
ord-d7ae6665ba524d8d83f6511f88bb0d7d
Source dataset
uspto-grants-2015_05
Patent number
US09023847B2

Reaction notes

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