tert-butyl (2S,4R)-2-[(4-amino-2-methoxyphenoxy)methyl]4-hydroxypyrrolidine-1-carboxylate → tert-butyl (2S,4R)-2-({4-[6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl]-2-methoxyphenoxy}methyl)-4-hydroxypyrrolidine-1-carboxylate

HRID 1181365Notes

Reaction equation

HRID 1181365 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([C:13]([O:15]C)=O)=[C:10](/[N:17]=[CH:18]/[N:19]([CH3:21])C)[CH:9]=2)=[CH:4][CH:3]=1.NC1[CH:43]=[CH:42][C:26]([O:27][CH2:28][C@@H:29]2[CH2:33][C@@H:32]([OH:34])[CH2:31][N:30]2[C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])=[C:25]([O:44][CH3:45])[CH:24]=1>C1(O)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[S:12][C:11]3[C:13](=[O:15])[N:19]([C:21]4[CH:43]=[CH:42][C:26]([O:27][CH2:28][C@@H:29]5[CH2:33][C@@H:32]([OH:34])[CH2:31][N:30]5[C:35]([O:37][C:38]([CH3:41])([CH3:39])[CH3:40])=[O:36])=[C:25]([O:44][CH3:45])[CH:24]=4)[CH:18]=[N:17][C:10]=3[CH:9]=2)=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 86594898tert-butyl (2S,4R)-2-[(4-amino-2-methoxyphenoxy)methyl]4-hydroxypyrrolidine-1-carboxylateHCID 178499302HCID 178499302, compound

Product 1

HCID 86594897tert-butyl (2S,4R)-2-({4-[6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl]-2-methoxyphenoxy}methyl)-4-hydroxypyrrolidine-1-carboxylateYield 41.8%

Reagents, catalysts & solvents 1

HCID 996PhenolSolvent

Procedure

Methyl 5-(4-chlorophenyl)-3-{[(E)-(dimethylamino)methylidene]amino}-2-thiophenecarboxylate (857 mg, 2.66 mmol) was mixed with tert-butyl (2S,4R)-2-[(4-amino-2-methoxyphenoxy)methyl]4-hydroxypyrrolidine-1-carboxylate (900 mg) in phenol (1.0 g) at 120° C. for 15 min. Workup and purification of the reaction mixture provided 650 mg of tert-butyl (2S,4R)-2-({4-[6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl]-2-methoxyphenoxy}methyl)-4-hydroxypyrrolidine-1-carboxylate. A portion of this material (105 mg, 0.179 mmol) was dissolved in a 1:1 mixture of dichloromethane and trifluoroacetic acid. The mixture was stirred at room temperature for 10 min and was then concentrated under reduced pressure. The residue was dissolved in dichloromethane and washed with a saturated solution of NaHCO3, brine, dried (Na2SO4) and concentrated to provide the title compound.

Workup

  1. customWorkup and purification of the reaction mixture

Sources & evidence

ORD record
ord-1bf348c52b264122bafe87d96cc4cc9b
Source dataset
uspto-grants-2007_10
Patent number
US07285557B2

Reaction notes

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