Triphenylphosphine → methyl (2R)-2-[(4-{[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-yl)oxy]propanoate

HRID 1162202Notes

Reaction equation

HRID 1162202 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][N:8]1[C:16]2[C:11](=[CH:12][C:13]([NH:17][C:18]3[C:27]4[C:26]([OH:28])=[CH:25][CH:24]=[CH:23][C:22]=4[N:21]=[CH:20][N:19]=3)=[CH:14][CH:15]=2)[CH:10]=[N:9]1.O[C@@H:30]([CH3:35])[C:31]([O:33][CH3:34])=[O:32].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][N:8]1[C:16]2[C:11](=[CH:12][C:13]([NH:17][C:18]3[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][C:26]=4[O:28][C@H:30]([CH3:35])[C:31]([O:33][CH3:34])=[O:32])[N:21]=[CH:20][N:19]=3)=[CH:14][CH:15]=2)[CH:10]=[N:9]1

Participants

5

Reactant 3

HCID 11776TriphenylphosphineHCID 94386methyl (S)-lactateHCID 1363467194-{[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-ol

Product 1

HCID 86627834methyl (2R)-2-[(4-{[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-yl)oxy]propanoateYield 74%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred partial solution of 4-{[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-ol (870 mg, 2.36 mmol), methyl (2S)-2-hydroxypropanoate (368 mg, 3.54 mmol) and triphenylphosphine (927 mg, 3.54 mmol) in DCM (20 ml) was added DTAD (814 mg, 3.54 mmol). The mixture was stirred for 1 hour, becoming a clear solution. The solution was extracted with 2N aqueous hydrogen chloride, discarding the organic phase. The aqueous phase was basified with aqueous ammonia and extracted with DCM. The organic phase was washed with brine, dried and evaporated to an oil which crystallised on trituration with ether to give methyl (2R)-2-[(4-{[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-yl)oxy]propanoate (789 mg, 74%); NMR spectrum (300 MHz) 1.70 (d, 3H), 3.78 (s, 3H), 5.51 (q, 1H), 5.76 (s, 2H), 6.95 (d, 1H), 7.16 (d, 1H), 7.28 (dd, 1H), 7.37 (d, 1H), 7.69 (m, 4H), 8.16 (s, 1H), 8.43 (s, 1H), 8.52 (s, 2H), 10.48 (s, 1H); Mass spectrum MH+ 455.

Workup

  1. extractionThe solution was extracted with 2N aqueous hydrogen chloride
  2. extractionextracted with DCM
  3. washThe organic phase was washed with brine
  4. customdried
  5. customevaporated to an oil which
  6. customcrystallised on trituration with ether

Sources & evidence

ORD record
ord-ce1a070996de4a31b3d67eb01a9293bc
Source dataset
uspto-grants-2010_10
Patent number
US07820683B2

Reaction notes

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