6-[(Cyclopropylmethyl)(propyl)amino]pyrimidine-4-carboxylic acid → HCID 67528819, compound

HRID 1946808Notes

Reaction equation

HRID 1946808 reaction equation
[CH:1]1([CH2:4][N:5]([CH2:15][CH2:16][CH3:17])[C:6]2[N:11]=[CH:10][N:9]=[C:8]([C:12]([OH:14])=O)[CH:7]=2)[CH2:3][CH2:2]1.[NH2:18][C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[N:24]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[N:23]=[C:22]2[CH2:35][CH2:36][C:37]([O:39][CH3:40])=[O:38]>C(Cl)Cl>[CH:1]1([CH2:4][N:5]([CH2:15][CH2:16][CH3:17])[C:6]2[N:11]=[CH:10][N:9]=[C:8]([C:12]([NH:18][C:19]3[CH:20]=[C:21]4[C:25](=[CH:26][CH:27]=3)[N:24]([C:28]([O:30][C:31]([CH3:32])([CH3:33])[CH3:34])=[O:29])[N:23]=[C:22]4[CH2:35][CH2:36][C:37]([O:39][CH3:40])=[O:38])=[O:14])[CH:7]=2)[CH2:2][CH2:3]1

Participants

4

Reactant 2

HCID 594470006-[(Cyclopropylmethyl)(propyl)amino]pyrimidine-4-carboxylic acid2×HCID 59447029tert-butyl 5-amino-3-(3-methoxy-3-oxopropyl)-1H-indazole-1-carboxylate2×

Product 1

HCID 67528819HCID 67528819, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 6-((cyclopropylmethyl)(propyl)amino)pyrimidine-4-carboxylic acid (Intermediate 21, 31 mg; 0.13 mmol) in DCM (5 ml) was treated with tert-butyl 5-amino-3-(3-methoxy-3-oxopropyl)-1H-indazole-1-carboxylate (Intermediate 45, 35 mg; 0.11 mmol) and polymer-supported Mukaiyama reagent (300 mg). After stirring at RT for 3 hours the mixture was filtered and washed with water. The organic phase was passed through a hydrophobic frit and the solvent removed in vacuo. The residue was purified by column chromatography (silica) eluting with petroleum ether containing increasing amounts of EtOAc to give tert-butyl 5-(6-((cyclopropylmethyl)(propyl)amino)pyrimidine-4-carboxamido)-3-(3-methoxy-3-oxopropyl)-1H-indazole-1-carboxylate. The intermediate was redissolved in DCM (2 ml) and treated with TFA (1 ml) and water (1 drop). After stirring at RT for 3 hours the solvent was removed in vacuo. The residue was partitioned between DCM and saturated sodium bicarbonate solution. The separated organic phase was passed through a hydrophobic frit and the solvent removed in vacuo. The residue was purified by column chromatography (silica) eluting with petroleum ether containing increasing amounts of EtOAc to give the title compound as an off-white solid.

Workup

  1. filtrationwas filtered
  2. washwashed with water
  3. customthe solvent removed in vacuo
  4. customThe residue was purified by column chromatography (silica)
  5. washeluting with petroleum ether containing
  6. temperatureincreasing amounts of EtOAc

Sources & evidence

ORD record
ord-e5c102ecaf764f119a341a130f289c9b
Source dataset
uspto-grants-2013_03
Patent number
US08399448B2

Reaction notes

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