4-Hydroxypyrrolidine → HCID 71115072, compound

HRID 1502327Notes

Reaction equation

Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]3[CH2:17][CH2:16]3)=[O:14])[N:8]=[CH:9]2)=[CH:4][CH:3]=1.[NH:18]1[CH2:22][CH2:21][CH:20]([OH:23])[CH2:19]1.C1(C2C=CC=CC=2)C=CC=CC=1P(C(C)(C)C)C(C)(C)C.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[OH:23][CH:20]1[CH2:21][CH2:22][N:18]([C:2]2[CH:11]=[C:10]3[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]4[CH2:17][CH2:16]4)=[O:14])[N:8]=[CH:9]3)=[CH:4][CH:3]=2)[CH2:19]1

Participants

Conditions

Temperature: 100 °C

Procedure

Dioxane (50 mL) was added to a mixture of N-(7-bromoisoquinolin-3-yl)cyclopropanecarbox-amide (200 mg, 0.69 mmol), pyrrolidin-3-ol (122 mg, 1.28 mmol), Pd2(dba)3 (120 mg, 0.14 mmol), biphenyl-2-yldi-tert-butylphosphine (78 mg, 0.25 mmol) and sodium tert-butoxide (80 mg, 0.82 mmol). After the reaction mixture was stirred at 100° C. under nitrogen overnight, the mixture was filtered, concentrated and purified by prep HPLC and prep TLC to give the product (33.1 mg, 16.2%). LCMS (ESI): RT (Min)=0.86, M+H+=298.0, method=B. 1H NMR (400 MHz, DMSO-d6) δ 10.58 (s, 1H), 8.82 (s, 1H), 8.22 (s, 1H), 7.65 (d, J=9.2 Hz, 1H), 7.19 (d, J=9.2 Hz, 1H), 6.80 (s, 1H), 4.99 (s, 1H), 4.45 (s, 1H), 3.50-3.48 (m, 1H), 3.45-3.36 (m, 2H), 3.20-3.12 (m, 1H), 2.25-2.05 (m, 1H), 1.85-2.05 (m, 2H), 0.80-0.75 (m, 4H).

Workup

filtrationthe mixture was filtered
concentrationconcentrated
custompurified by prep HPLC

Sources & evidence

ORD record: ord-1b5055584cf84f48af518f79eca9b2f0
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09206175B2

Reaction notes

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