Diisopropylethylamine → HCID 70983295, compound

HRID 1479190Notes

Reaction equation

HRID 1479190 reaction equation
Cl.[CH3:2][N:3]1[CH2:8][CH2:7][N:6]([C:9]2[CH:17]=[CH:16][C:12]([C:13](Cl)=[O:14])=[CH:11][CH:10]=2)[CH2:5][CH2:4]1.CN1CCN(C2C=CC(C(O)=O)=CC=2)CC1.CCN(C(C)C)C(C)C.[C:43]([O:47][C:48]([N:50]1[C:58]2[C:53](=[CH:54][CH:55]=[C:56]([O:59][CH2:60][CH2:61][O:62][CH2:63][C:64]3[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=3)[CH:57]=2)[C:52]([NH2:70])=[N:51]1)=[O:49])([CH3:46])([CH3:45])[CH3:44]>C1COCC1>[C:43]([O:47][C:48]([N:50]1[C:58]2[C:53](=[CH:54][CH:55]=[C:56]([O:59][CH2:60][CH2:61][O:62][CH2:63][C:64]3[CH:65]=[CH:66][CH:67]=[CH:68][CH:69]=3)[CH:57]=2)[C:52]([NH:70][C:13](=[O:14])[C:12]2[CH:16]=[CH:17][C:9]([N:6]3[CH2:7][CH2:8][N:3]([CH3:2])[CH2:4][CH2:5]3)=[CH:10][CH:11]=2)=[N:51]1)=[O:49])([CH3:46])([CH3:44])[CH3:45]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 7365324-(4-Methylpiperazin-1-yl)benzoic acidHCID 70983155HCID 70983155, compoundHCID 86712573HCID 86712573, compound

Product 1

HCID 70983295HCID 70983295, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

A mixture of 4-(4-methyl-piperazin-1-yl)-benzoyl chloride hydrochloride, prepared from 248 mg (1.13 mmol) of 4-(4-methyl-piperazin-1-yl)-benzoic acid as described above in preparation 3, and DIPEA (0.386 ml, 2.25 mmol) in dry THF (10 ml) was treated dropwise at r.t., under argon atmosphere, with a solution of 3-amino-6-(2-benzyloxy-ethoxy)-indazole-1-carboxylic acid tert-butyl ester (143 mg, 0.374 mmol) in 10 ml of dry THF. The reaction mixture was heated up to 50° C. and stirred for 12 h. The volatiles were removed under reduced pressure, the residue taken up in DCM (100 ml) and washed with a saturated solution of NaHCO3 (75 ml). The organic layer was separated, dried over sodium sulfate and evaporated to dryness and the crude residue purified by flash chromatography over silica gel eluting with DCM/MeOH 98:2 then 90:10 affording 124 mg (yield: 57%) of the title compound as a white solid.

Workup

  1. customThe volatiles were removed under reduced pressure
  2. washwashed with a saturated solution of NaHCO3 (75 ml)
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. customevaporated to dryness
  6. customthe crude residue purified by flash chromatography over silica gel eluting with DCM/MeOH 98:2

Sources & evidence

ORD record
ord-1dc8da2737ae4550a6a545af06433016
Source dataset
uspto-grants-2016_08
Patent number
US09408850B2

Reaction notes

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