Diisopropylamine → HCID 71544290, compound

HRID 2406463Notes

Reaction equation

[CH:1]([NH:4][CH:5]([CH3:7])C)([CH3:3])C.[Li][CH2:9][CH2:10][CH2:11][CH3:12].[NH:13]1[CH:17]=[C:16]([C:18]2[S:19][CH:20]=[CH:21][N:22]=2)[CH:15]=[N:14]1.C1C[O:26]CC1>C(C1C=CN=CC=1)(=O)C>[NH:13]1[CH:17]=[C:16]([C:18]2[S:19][C:20]([C:11]([C:12]3[CH:3]=[CH:1][N:4]=[CH:5][CH:7]=3)([OH:26])[CH2:10][CH3:9])=[CH:21][N:22]=2)[CH:15]=[N:14]1

Participants

Conditions

Temperature: -10 °C

Procedure

To a stirred solution of diisopropylamine (0.28 mL, 1.9 mmol) in THF (10 mL) at −60° C. was added n-BuLi (1.6 M, 2.48 mL) slowly. The reaction mixture was stirred for 30 min at −10° C., cooled to −78° C., and a solution 2-(1H-pyrazol-4-yl)thiazole (200 mg, 1.3 mmol) in THF (5 mL) added dropwise for 30 minutes. 4-Acetyl pyridine (0.07 mL, 0.000674 mmol) in THF (2 mL) was then added and the reaction mixture stirred for additional 1 hour at −78° C. The work up was done as described in Example 23, Step 2, to obtain crude product. The crude product was purified by preparative TLC (mobile phase: 70% ethyl acetate in hexane) to give racemic 1-(2-(1H-pyrazol-4-yl)thiazol-5-yl)-1-(pyridin-4-yl)propan-1-ol as pale yellow solid (134 mg, 35% yield) in 99% HPLC purity. 1H NMR (400 MHz, DMSO-d6): δ 13.18 (br s, 1H), 8.50 (d, 2H), 8.22 (br s, 1H), 7.85 (br s, 1H), 7.63 (s, 1H), 7.43 (d, 2H), 6.28 (s, 1H), 2.32-2.24 (m, 2H), 0.75 (t, 3H); LC-MS m/z calculated for [M+H]+ 287.09, found 287.1.

Workup

temperaturecooled to −78° C.
stirringthe reaction mixture stirred for additional 1 hour at −78° C
customto obtain crude product
customThe crude product was purified by preparative TLC (mobile phase: 70% ethyl acetate in hexane)

Sources & evidence

ORD record: ord-c175e2ed59d742debd132b3962f5f45d
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08809372B2

Reaction notes

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