Ethylamine → HCID 178465148, compound

HRID 1852540Notes

Reaction equation

HRID 1852540 reaction equation
[N:1]1([C:10]2[C:15]([Cl:16])=[CH:14][N:13]=[C:12]([NH:17][C@H:18]3[CH2:23][CH2:22][C@H:21]([C:24]([OH:26])=O)[CH2:20][CH2:19]3)[N:11]=2)[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[N:2]1.[CH2:27]([NH2:29])[CH3:28].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>C1COCC1>[CH2:27]([NH:29][C:24]([C@H:21]1[CH2:22][CH2:23][C@H:18]([NH:17][C:12]2[N:11]=[C:10]([N:1]3[C:5]4[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=4[N:3]=[N:2]3)[C:15]([Cl:16])=[CH:14][N:13]=2)[CH2:19][CH2:20]1)=[O:26])[CH3:28]

Participants

6

Reactant 4

HCID 6341EthylamineHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 178525762HCID 178525762, compound

Product 1

HCID 178465148HCID 178465148, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of trans-4-(4-benzotriazol-1-yl-5-chloro-pyrimidin-2-ylamino)-cyclohexane-carboxylic acid (70 mg, 0.17 mmol), ethyl amine (21 μL, 0.26 mmol), BOP (114 mg, 0.26 mmol) and DIPEA (59 μL, 0.34 mmol) in THF (60 mL) was stirred at RT for 2 days. The white solid formed was removed by filtration and the filtrate was diluted with water (25 mL) and extracted 3 times with a mixture isopropanol/chloroform (1/1, 20 mL). The combined organic extracts were dried over Na2SO4, filtered and evaporated under reduced pressure to give an off white residue that was purified via flash chromatography (DCM/MeOH, 98/2) to afford 68 mg (quantitative yield) of trans-4-(4-benzotriazol-1-yl-5-chloro-pyrimidin-2-ylamino)-cyclohexane-carboxylic acid ethylamide as a white solid. MS: 400.17 (M+1)+, 372.17 ((M+1)+−28). 1H NMR (250 MHz, CD3OD) δ ppm: 8.55 (1 H, s), 8.09-8.21 (2 H, m), 7.69 (1 H, dd, J=7.50 Hz), 7.55 (1 H, dd, J=7.50 Hz), 3.71-3.88 (1 H, m), 3.18 (2 H, q, J=7.29 Hz), 2.10-2.25 (3 H, m), 1.82-1.95 (2 H, m), 1.50-1.71 (2 H, m), 1.26-1.48 (2 H, m), 1.10 (3 H, t, J=7.29 Hz).

Workup

  1. customThe white solid formed
  2. customwas removed by filtration
  3. additionthe filtrate was diluted with water (25 mL)
  4. extractionextracted 3 times with a mixture isopropanol/chloroform (1/1, 20 mL)
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customto give an off white residue that
  9. customwas purified via flash chromatography (DCM/MeOH, 98/2)

Sources & evidence

ORD record
ord-6349c0e8ef1d401ea091f70d29882630
Source dataset
uspto-grants-2015_02
Patent number
US08962622B2

Reaction notes

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