Diisopropylethylamine → 4-{3-[7-(3,4-Dimethoxy-phenylamino)-thiazolo[5,4-d]pyrimidin-5-yl]-benzoyl}-[1,4]-diazepane-1-carboxylic acid tert-butyl ester

HRID 1409999Notes

Reaction equation

HRID 1409999 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:29]=[CH:28][S:27][C:14]=3[N:15]=[C:16]([C:18]3[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=3)[C:21]([OH:23])=O)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].CCN(C(C)C)C(C)C.[N:39]1([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:45][CH2:44][CH2:43][NH:42][CH2:41][CH2:40]1.C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1>C1COCC1>[C:49]([O:48][C:46]([N:39]1[CH2:45][CH2:44][CH2:43][N:42]([C:21](=[O:23])[C:20]2[CH:24]=[CH:25][CH:26]=[C:18]([C:16]3[N:17]=[C:12]([NH:11][C:5]4[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=4)[C:13]4[N:29]=[CH:28][S:27][C:14]=4[N:15]=3)[CH:19]=2)[CH2:41][CH2:40]1)=[O:47])([CH3:52])([CH3:50])[CH3:51]

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 2756058Tert-butyl 1,4-diazepane-1-carboxylateHCID 665513433-(7-(3,4-Dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoic acid

Product 1

HCID 683794114-{3-[7-(3,4-Dimethoxy-phenylamino)-thiazolo[5,4-d]pyrimidin-5-yl]-benzoyl}-[1,4]-diazepane-1-carboxylic acid tert-butyl esterYield 95.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 3-[7-(3,4-dimethoxy-phenylamino)-thiazolo[5,4-d]pyrimidin-5-yl]-benzoic acid (95 mg, 0.23 mmol) in 10 mL of THF was added DIEA (30 mg, 0.23 mmol) at room temperature. Then tert-butyl 1,4-diazepane-1-carboxylate (60 mg, 0.3 mmol), BOP-Cl (76 mg, 0.3 mmol) and DIEA (59 mg, 0.46 mmol) were added and the reaction mixture was stirred at room temperature for 16 hours. The solvent was evaporated and the residue was purified by silica gel chromatography (silica gel 200-300 mesh, methanol:CH2Cl2=1:100) to give 4-{3-[7-(3,4-dimethoxy-phenylamino)-thiazolo[5,4-d]pyrimidin-5-yl]-benzoyl}-[1,4]-diazepane-1-carboxylic acid tert-butyl ester (130 mg, 95.7%) as a yellow solid. LC-MS: 591.2 [M+H]+, tR=1.81 min.

Workup

  1. customThe solvent was evaporated
  2. customthe residue was purified by silica gel chromatography (silica gel 200-300 mesh, methanol:CH2Cl2=1:100)

Sources & evidence

ORD record
ord-3a6580160678497498a7e79423444f5c
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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