(1-(Prop-2-yn-1-yl)piperidin-4-yl)methanol → N-(3-fluoro-4-(2-(3-(4-(hydroxymethyl)piperidin-1-yl)prop-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 1676307Notes

Reaction equation

HRID 1676307 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:19]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)[C:20]([C:22]2([C:25]([NH2:27])=[O:26])[CH2:24][CH2:23]2)=[O:21])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16](I)[S:17][C:10]=12.[CH2:35]([N:38]1[CH2:43][CH2:42][CH:41]([CH2:44][OH:45])[CH2:40][CH2:39]1)[C:36]#[CH:37]>>[F:1][C:2]1[CH:3]=[C:4]([N:19]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)[C:20]([C:22]2([C:25]([NH2:27])=[O:26])[CH2:24][CH2:23]2)=[O:21])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:37]#[C:36][CH2:35][N:38]3[CH2:43][CH2:42][CH:41]([CH2:44][OH:45])[CH2:40][CH2:39]3)[S:17][C:10]=12

Participants

3

Reactant 2

HCID 18616662(1-(Prop-2-yn-1-yl)piperidin-4-yl)methanolHCID 67347909N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Product 1

HCID 67347182N-(3-fluoro-4-(2-(3-(4-(hydroxymethyl)piperidin-1-yl)prop-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamideYield 32.1%

Procedure

Prepared from N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (Example 12, Step A, 20 mg, 0.0338 mmol) and (1-(prop-2-ynyl)piperidin-4-yl)methanol (10.4 mg, 0.0676 mmol) using the procedure described for Example 6, Step B. The crude was purified by preparative TLC (1 mm thickness, Rf=0.72) eluting with 20% MeOH/DCM. The product was obtained as a beige powder (6.7 mg, 32%). HPLC: 100% purity (220 nm); LRMS (APCI+): 100% purity, 220 nm, m/z 617 (M+1) detected; 1H NMR (400 MHz, CDCl3) δ 10.14 (s, 1H), 8.48 (d, J=5 Hz, 1H), 8.42 (s, 1H), 7.75 (m, 1H), 7.59 (s, 1H), 7.47 (m, 2H), 7.28 (m, 1H), 7.21 (m, 1H), 7.05 (t, J=9 Hz, 2H), 6.52 (d, J=5 Hz, 1H), 3.65 (s, 2H), 3.53 (d, J=6 Hz, 2H), 3.09 (m, 2H), 2.38 (m, 2H), 1.86 (m, 2H), 1.81 (m, 2H), 1.64 (m, 2H), 1.55 (m, 1H), 1.45 (m, 2H).

Workup

  1. customThe crude was purified by preparative TLC (1 mm thickness, Rf=0.72)
  2. washeluting with 20% MeOH/DCM

Sources & evidence

ORD record
ord-3f5877f8d6514172a537c9bd4af39b77
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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