Triphenylphosphine → 3-Oxazolo[5,4-b]pyridin-2-yl-5-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]pyridin-2-amine

HRID 908440Notes

Reaction equation

HRID 908440 reaction equation
N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.[NH2:17][C:18]1[N:23]=[CH:22][C:21]([C:24]2[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][CH:25]=2)=[CH:20][C:19]=1[C:31]1[O:32][C:33]2[C:38]([N:39]=1)=[CH:37][CH:36]=[CH:35][N:34]=2.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N:59]1([CH2:64][CH2:65][CH2:66]O)[CH2:63][CH2:62][CH2:61][CH2:60]1>ClCCl.CN(C=O)C>[N:39]1[C:38]2[C:33](=[N:34][CH:35]=[CH:36][CH:37]=2)[O:32][C:31]=1[C:19]1[C:18]([NH2:17])=[N:23][CH:22]=[C:21]([C:24]2[CH:29]=[CH:28][C:27]([O:30][CH2:66][CH2:65][CH2:64][N:59]3[CH2:63][CH2:62][CH2:61][CH2:60]3)=[CH:26][CH:25]=2)[CH:20]=1

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 2093421-PyrrolidinepropanolHCID 673890074-(6-Amino-5-oxazolo[5,4-b]pyridin-2-yl-3-pyridyl)phenol

Product 1

HCID 673885153-Oxazolo[5,4-b]pyridin-2-yl-5-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]pyridin-2-amineYield 26.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of di-tert-butyl azodicarboxylate (DTAD) (227 mg) in dichloromethane (1 ml) was added to a stirred solution of 4-(6-amino-5-oxazolo[5,4-b]pyridin-2-yl-3-pyridyl)phenol (100 mg), polystyrene bound triphenylphosphine (330 mg, 3 mmol/g) and 3-pyrrolidin-1-ylpropan-1-ol (64 mg) in DMF (2 ml) at room temperature under argon. The resulting suspension was stirred at room temperature for 2 hours. The mixture was filtered and the resulting solid was washed with methanol. The filtrates were combined, concentrated to dryness and diluted with DCM/TFA (1 ml: 1 ml). The mixture was stirred for 30 min and concentrated. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 micron silica, 19 mm diameter, 100 mm length, flow rate of 40 ml/minute) and decreasingly polar mixtures of water (containing 1% acetic acid) and Methanol as eluent. The fractions containing the desired compound were evaporated to dryness to afford 3-oxazolo[5,4-b]pyridin-2-yl-5-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]pyridin-2-amine (36 mg) as a solid. NMR Spectrum: (DMSOd6) 1.86 (bs, 4H), 2.03-2.15 (m, 2H), 3.02-3.33 (m partially hidden by H2O, 6H), 4.11 (t, 2H), 7.06 (d, 2H), 7.53 (dd, 1H), 7.68 (d, 2H), 7.77 (bs, 2H), 8.30 (dd, 1H), 8.40 (dd, 1H), 8.46 (d, 1H), 8.58 (d, 1H); Mass spectrum: M+H+ 416. The 4-(6-amino-5-oxazolo[5,4-b]pyridin-2-yl-3-pyridyl)phenol used as starting material was made as follows:

Workup

  1. customat room temperature
  2. filtrationThe mixture was filtered
  3. washthe resulting solid was washed with methanol
  4. concentrationconcentrated to dryness
  5. additiondiluted with DCM/TFA (1 ml: 1 ml)
  6. stirringThe mixture was stirred for 30 min
  7. concentrationconcentrated
  8. customThe reaction mixture was purified by preparative HPLC
  9. additionThe fractions containing the desired compound
  10. customwere evaporated to dryness

Sources & evidence

ORD record
ord-410c2818cb7740d988e62f52aef05418
Source dataset
uspto-grants-2011_09
Patent number
US08017611B2

Reaction notes

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