Diisopropylamine → (3-{4-[1-(3-Fluoro-benzyl)-1H-indazol-5-ylamino]-quinazolin-6-yl}-prop-2-ynyl)-carbamic acid tert-butyl ester

HRID 415024Notes

Reaction equation

HRID 415024 reaction equation
Cl.[F:2][C:3]1[CH:4]=[C:5]([CH:28]=[CH:29][CH:30]=1)[CH2:6][N:7]1[C:15]2[C:10](=[CH:11][C:12]([NH:16][C:17]3[C:26]4[C:21](=[CH:22][CH:23]=[C:24](I)[CH:25]=4)[N:20]=[CH:19][N:18]=3)=[CH:13][CH:14]=2)[CH:9]=[N:8]1.[C:31]([O:35][C:36](=[O:41])[NH:37][CH2:38][C:39]#[CH:40])([CH3:34])([CH3:33])[CH3:32].N(C(C)C)C(C)C>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[C:31]([O:35][C:36](=[O:41])[NH:37][CH2:38][C:39]#[C:40][C:24]1[CH:25]=[C:26]2[C:21](=[CH:22][CH:23]=1)[N:20]=[CH:19][N:18]=[C:17]2[NH:16][C:12]1[CH:11]=[C:10]2[C:15](=[CH:14][CH:13]=1)[N:7]([CH2:6][C:5]1[CH:28]=[CH:29][CH:30]=[C:3]([F:2])[CH:4]=1)[N:8]=[CH:9]2)([CH3:34])([CH3:33])[CH3:32]

Participants

7

Reactant 3

HCID 7912DiisopropylamineHCID 11073648tert-butyl N-(prop-2-yn-1-yl)carbamateHCID 66623800[1-(3-Fluoro-benzyl)-1H-indazol-5-yl]-(6-iodo-quinazolin-4-yl)-amine hydrochloride

Product 1

HCID 66623769(3-{4-[1-(3-Fluoro-benzyl)-1H-indazol-5-ylamino]-quinazolin-6-yl}-prop-2-ynyl)-carbamic acid tert-butyl esterYield 89.3%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

[1-(3-Fluoro-benzyl)-1H-indazol-5-yl]-(6-iodo-quinazolin-4-yl)-amine hydrochloride (0.334 g, 0.628 mmol) and Prop-2-ynyl-carbamic acid tert-butyl ester (113 mg, 1.16 equiv.) is treated with i-Pr2NH (2 equiv.) in dry THF (4 ml) under N2. Pd(PPh3)4 (25 mg, 0.0356 mmol, 5.7 mol %) and solid CuI (5 mol %) are added next, and the mixture is stirred at r.t. for 3 hours. Workup: THF is removed under reduced pressure and DCM (10 ml) is added. The organic layer is washed with sat. aq. NH4Cl solution and brine, dried and concentrated. Chromatography on silica (EtOAc/hexanes) affords the desired pure product (293 mg, 89%).

Workup

  1. customWorkup: THF is removed under reduced pressure and DCM (10 ml)
  2. additionis added
  3. washThe organic layer is washed with sat. aq. NH4Cl solution and brine
  4. customdried
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-5957178150f44cb5b1bad6373a09372f
Source dataset
uspto-grants-2012_01
Patent number
US08088766B2

Reaction notes

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