4-Methylmorpholine → HCID 24983479, compound

HRID 1676267Notes

Reaction equation

FC1C=CC(NC(C2(C(O)=O)CC2)=O)=CC=1.CN1CCOCC1.Cl[C:25]([O:27][CH2:28][CH:29]([CH3:31])[CH3:30])=[O:26].[CH2:32]([N:34]([CH2:55][CH3:56])[CH2:35][C:36]#[C:37][C:38]1[S:46][C:45]2[C:40](=[N:41][CH:42]=[CH:43][C:44]=2[O:47][C:48]2[CH:53]=[CH:52][C:51]([NH2:54])=[CH:50][CH:49]=2)[CH:39]=1)[CH3:33]>C1COCC1>[CH2:55]([N:34]([CH2:32][CH3:33])[CH2:35][C:36]#[C:37][C:38]1[S:46][C:45]2[C:40](=[N:41][CH:42]=[CH:43][C:44]=2[O:47][C:48]2[CH:49]=[CH:50][C:51]([NH:54][C:25](=[O:26])[O:27][CH2:28][CH:29]([CH3:31])[CH3:30])=[CH:52][CH:53]=2)[CH:39]=1)[CH3:56]

Participants

Conditions

Temperature: -78 °C

Procedure

A 25 mL, single-neck, round-bottomed flask was charged with 1-((4-fluorophenyl)carbamoyl)cyclopropanecarboxylic acid (42 mg, 0.1694 mmol) and THF (2 mL) under nitrogen and cooled to −78° C. on a dry ice bath. N-methylmorpholine (0.037 mL, 0.34 mmol), and isobutyl chloroformate (0.019 ml, 0.15 mmol) were added. After 15 minutes 4-(2-(3-(diethylamino)prop-1-ynyl)thieno[3,2-b]pyridin -7-yloxy)benzenamine (40 mg, 0.11 mmol) in THF (1 mL) was added, and the reaction was allowed to warm to room temperature overnight. The reaction mixture was concentrated and the residue was purified on a Biotage 15M column (95:5 EtOAc/MeOH). The product was a white waxy solid (0.8 mg, 2%). 1H NMR (CDCl3, 400 MHz) δ 8.47 (d, J=5.5 Hz, 1H), 7.57 (s, 1H), 7.49 (m, 2H), 7.14 (m, 2H), 6.68 (br s, 1H), 6.54 (d, J=5.5 Hz, 1H), 3.98 (d, J=6.6 Hz, 2H), 3.72 (s, 2H), 2.65 (q, J=7, 14 Hz, 4H), 2.00 (m, 1H), 1.14 (t, J=7.0 Hz, 6H), 0.99 (d, J=7.0 Hz, 6H). LRMS (ESI pos) m/e 452 (M+1).

Workup

temperatureto warm to room temperature overnight
concentrationThe reaction mixture was concentrated
customthe residue was purified on a Biotage 15M column (95:5 EtOAc/MeOH)

Sources & evidence

ORD record: ord-cd585b143c4e4563b41dd8156140537d
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08003662B2

Reaction notes

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