Lithium Hydroxide → HCID 59264675, compound

HRID 646448Notes

Reaction equation

HRID 646448 reaction equation
C([C@@H]([C@H](C(O)=O)O)O)(O)=O.C([O:13][C:14]([C:16]1[CH:17]=[N:18][N:19]([C:22]2[CH:27]=[CH:26][C:25]([C:28]([N:30]3[CH2:34][CH2:33][CH2:32][C@H:31]3[CH2:35][N:36]3[CH2:40][CH2:39][CH2:38][CH2:37]3)=[O:29])=[CH:24][CH:23]=2)[C:20]=1[CH3:21])=O)C.[OH-].[Li+].[Li].[NH:44]1[CH2:48][CH2:47][CH2:46][CH2:45]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)CC)C>CO.CN(C)C=O.O>[CH3:21][C:20]1[N:19]([C:22]2[CH:27]=[CH:26][C:25]([C:28]([N:30]3[CH2:34][CH2:33][CH2:32][C@H:31]3[CH2:35][N:36]3[CH2:37][CH2:38][CH2:39][CH2:40]3)=[O:29])=[CH:24][CH:23]=2)[N:18]=[CH:17][C:16]=1[C:14]([N:44]1[CH2:48][CH2:47][CH2:46][CH2:45]1)=[O:13]

Participants

10

Reactant 6

HCID 3939Lithium HydroxideHCID 8471TriethylamineHCID 31268PyrrolidineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 3028194LithiumHCID 68544630HCID 68544630, compound

Product 1

HCID 59264675HCID 59264675, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

5-Methyl-1-[4-(2-(S)-pyrrolidin-1-ylmethyl-pyrrolidine-1-carbonyl)-phenyl]-1H-pyrazole-4-carboxylic acid ethyl ester from Example 56 (270 mg, 0.66 mmole) is hydrolysed using lithium hydroxide in aqueous methanol and the resulting lithium salt recovered by freeze drying. The lithium salt, pyrrolidine (140 mg, 2 mmole), TBTU (325 mg, 1 mmole) and triethylamine (212 mg, 2 mmole) are dissolved in dimethylformamide (10 mL) and the mixture is stirred for 18 hours. The reaction is diluted with water, extracted with ethyl acetate, washed with water, dried and evaporated to dryness. The product is purified by chromatography on silica gel using 10% methanol in dichloromethane and the title compound recovered by crystallization from ethyl acetate. MS (m/e): 436.3 (M+1).

Workup

  1. customthe resulting lithium salt recovered by freeze
  2. customdrying
  3. extractionextracted with ethyl acetate
  4. washwashed with water
  5. customdried
  6. customevaporated to dryness
  7. customThe product is purified by chromatography on silica gel using 10% methanol in dichloromethane
  8. customthe title compound recovered by crystallization from ethyl acetate

Sources & evidence

ORD record
ord-670ad948e76b46a8a827f9b1e1b5dc5b
Source dataset
uspto-grants-2010_04
Patent number
US07705025B2

Reaction notes

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