Piperidin-4-ol → (4-{4-[8-(1-Hydroxy-1-methyl-ethyl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-cyclohexyl)-(4-hydroxy-piperidin-1-yl)-methanone

HRID 1046531Notes

Reaction equation

HRID 1046531 reaction equation
[OH:1][C:2]([C:5]1[C:6]2[N:7]([C:11]([C:14]3[CH:19]=[CH:18][N:17]=[C:16]([NH:20][CH:21]4[CH2:26][CH2:25][CH:24]([C:27](O)=[O:28])[CH2:23][CH2:22]4)[N:15]=3)=[CH:12][N:13]=2)[CH:8]=[CH:9][CH:10]=1)([CH3:4])[CH3:3].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.[NH:66]1[CH2:71][CH2:70][CH:69]([OH:72])[CH2:68][CH2:67]1>CN(C=O)C>[OH:1][C:2]([C:5]1[C:6]2[N:7]([C:11]([C:14]3[CH:19]=[CH:18][N:17]=[C:16]([NH:20][CH:21]4[CH2:26][CH2:25][CH:24]([C:27]([N:66]5[CH2:71][CH2:70][CH:69]([OH:72])[CH2:68][CH2:67]5)=[O:28])[CH2:23][CH2:22]4)[N:15]=3)=[CH:12][N:13]=2)[CH:8]=[CH:9][CH:10]=1)([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 79341Piperidin-4-olHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 666163124-{4-[8-(1-Hydroxy-1-methyl-ethyl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-cyclohexanecarboxylic acid

Product 1

HCID 46896570(4-{4-[8-(1-Hydroxy-1-methyl-ethyl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-cyclohexyl)-(4-hydroxy-piperidin-1-yl)-methanoneYield 66.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-{4-[8-(1-hydroxy-1-methyl-ethyl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-cyclohexanecarboxylic acid (0.175 g), BOP (0.39 g), DIEA (0.23 mL), and piperidin-4-ol (67 mg) in DMF (5 mL) was stirred at RT overnight. The resulting solid was filtered and dried, purified by ISCO using 100% DCM to 20% MeOH/DCM. The fractions were collected and concentrated, then titurated with EtOAc, and the resulting solid filtered and dried at 50° C. overnight to provide (4-{4-[8-(1-hydroxy-1-methyl-ethyl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-cyclohexyl)-(4-hydroxy-piperidin-1-yl)-methanone (Compound 2, 140.4 mg). Mp=188.0-190.0° C.

Workup

  1. filtrationThe resulting solid was filtered
  2. customdried
  3. custompurified by ISCO
  4. customThe fractions were collected
  5. concentrationconcentrated
  6. filtrationthe resulting solid filtered
  7. customdried at 50° C. overnight

Sources & evidence

ORD record
ord-e02cf24855af4b21a261132202f6e511
Source dataset
uspto-grants-2013_10
Patent number
US08569306B2

Reaction notes

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