3-Amino-1,2-propanediol → 3-(3-tert-butyl-5-{[({2-fluoro-4-[(2-methylpyridin-4-yl)oxy]phenyl}amino)carbonyl]-amino}-1H-pyrazol-1-yl)-N-(2,3-dihydroxypropyl)benzamide

HRID 221908Notes

Reaction equation

HRID 221908 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]3[CH:26]=[CH:25][N:24]=[C:23]([CH3:27])[CH:22]=3)=[CH:16][C:15]=2[F:28])=[O:12])[N:7]([C:29]2[CH:30]=[C:31]([CH:35]=[CH:36][CH:37]=2)[C:32](O)=[O:33])[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH2:38][CH2:39][CH:40]([OH:43])[CH2:41][OH:42].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C1C=CN=CC=1.C1COCC1.C(Cl)Cl.O.C(OCC)(=O)C>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]3[CH:26]=[CH:25][N:24]=[C:23]([CH3:27])[CH:22]=3)=[CH:16][C:15]=2[F:28])=[O:12])[N:7]([C:29]2[CH:30]=[C:31]([CH:35]=[CH:36][CH:37]=2)[C:32]([NH:38][CH2:39][CH:40]([OH:43])[CH2:41][OH:42])=[O:33])[N:6]=1)([CH3:2])([CH3:4])[CH3:3]

Participants

10

Reactant 4

HCID 735613-Amino-1,2-propanediolHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 536301863-(3-Tert-butyl-5-{3-[2-fluoro-4-(2-methyl-pyridin-4-yloxy)-phenyl]-ureido}-pyrazol-1-yl)-benzoic acid

Product 1

HCID 116927143-(3-tert-butyl-5-{[({2-fluoro-4-[(2-methylpyridin-4-yl)oxy]phenyl}amino)carbonyl]-amino}-1H-pyrazol-1-yl)-N-(2,3-dihydroxypropyl)benzamideYield 20%

Reagents, catalysts & solvents 5

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3-(3-tert-butyl-5-{3-[2-fluoro-4-(2-methyl-pyridin-4-yloxy)-phenyl]-ureido}-pyrazol-1-yl)-benzoic acid (100 mg, 0.20 mmol), 3-aminopropane-1,2-diol (22 mg, 0.24 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (46 mg, 0.24 mmol), 4-dimethylaminopyridine (29 mg, 0.24 mmol) and 1-hydroxybenzotriazole (32 mg, 0.24 mmol) in THF and DCM was stirred at room temperature overnight. Ethyl acetate and water were added, and the organic phase was washed with brine, dried over MgSO4, and evaporated at reduced pressure. HPLC purification (10-90% aqueous acetonitrile) afforded pure title compound (23 mg, 20%). 1H-NMR (DMSO-d6) δ 8.97 (s, 1H), 8.91 (s, 1H), 8.55 (t, J=5.7 Hz, 1H), 8.29 (d, J=7.2 Hz, 1H), 8.11 (t, J=9.0 Hz, 1H), 7.98 (s, 1H), 7.89 (d, J=7.2 Hz, 1H), 7.64-7.58 (m, 2H), 7.18 (d, J=9.0 Hz, 1H), 6.94 (d, J=12.0 Hz, 1H), 6.76 (s, 1H), 4.81 (s, 1H), 4.57 (s, 1H), 3.62 (t, J=5.7 Hz, 1H). 3.40 (m, 2H), 3.18 (m, 2H), 2.36 (s, 3H), 1.80 (s, 9H); MS LC-MS [M+H]+=577.3, RT=1.54 min.

Workup

  1. washthe organic phase was washed with brine
  2. dry with materialdried over MgSO4
  3. customevaporated at reduced pressure
  4. customHPLC purification (10-90% aqueous acetonitrile)

Sources & evidence

ORD record
ord-8e63b27600ba4efe9c684cc9aadcf640
Source dataset
uspto-grants-2012_06
Patent number
US08207166B2

Reaction notes

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