1-Pyrrolidineethanamine → HCID 86634764, compound

HRID 911045Notes

Reaction equation

HRID 911045 reaction equation
[Br:1][C:2]1[C:3]([O:22][C:23]2[CH:24]=[C:25]([CH:29]=[CH:30][C:31]=2[Cl:32])[C:26]([OH:28])=O)=[CH:4][C:5]([NH:8][C:9]2[S:10][CH:11]=[C:12]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[N:13]=2)=[N:6][CH:7]=1.[N:33]1([CH2:38][CH2:39][NH2:40])[CH2:37][CH2:36][CH2:35][CH2:34]1.C(N(CC)C(C)C)(C)C>C1COCC1>[ClH:32].[ClH:32].[Br:1][C:2]1[C:3]([O:22][C:23]2[CH:24]=[C:25]([CH:29]=[CH:30][C:31]=2[Cl:32])[C:26]([NH:40][CH2:39][CH2:38][N:33]2[CH2:37][CH2:36][CH2:35][CH2:34]2)=[O:28])=[CH:4][C:5]([NH:8][C:9]2[S:10][CH:11]=[C:12]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[N:13]=2)=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 13441-PyrrolidineethanamineHCID 81531DiisopropylethylamineHCID 57898996HCID 57898996, compound

Product 1

HCID 86634764HCID 86634764, compoundYield 159.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A vial was charged with 3-(5-bromo-2-(4-phenethylthiazol-2-ylamino)pyridin-4-yloxy)-4-chlorobenzoic acid (0.050 g, 0.0942 mmol), 1-pyrrolidine ethanamine (0.013 g, 0.113 mmol), N,N-diisopropylethylamine (0.0328 mL, 0.188 mmol), and THF (3 mL). Diethyl cyanophosphononate (0.0239 g, 0.132 mmol) was added and the reaction was stirred for 4 hours at ambient temperature. The reaction mixture was concentrated and the residue was partitioned between water and ethyl acetate. The organic later was dried and concentrated, and the crude material was purified by preparative TLC using 5% ammoniated methanol in DCM. The isolated material was treated with 2M HCl in ether and the isolated solids were dried in vacuum to give the title compound (0.035 g, 51.5% yield) as a light yellow solid. 1H NMR (CDCl3) δ 8.99 (s, 1H), 8.36 (s, 1H), 7.96 (m, 2H), 7.57 (m, 1H), 7.25 (m, 1H), 7.15 (m, 3H), 6.70 (s, 1H), 6.30 (s, 1H), 3.85 (m, 4H), 3.35 (m, 2H), 2.93 (m, 6H), 2.14 (m, 4H).

Workup

  1. additionDiethyl cyanophosphononate (0.0239 g, 0.132 mmol) was added
  2. concentrationThe reaction mixture was concentrated
  3. customthe residue was partitioned between water and ethyl acetate
  4. customThe organic later was dried
  5. concentrationconcentrated
  6. customthe crude material was purified by preparative TLC
  7. additionThe isolated material was treated with 2M HCl in ether
  8. customthe isolated solids were dried in vacuum

Sources & evidence

ORD record
ord-d3b0b700432b446c8de2092849ca6b3a
Source dataset
uspto-grants-2011_09
Patent number
US08022222B2

Reaction notes

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