Trifluoroacetylation of pyrrolo[1,2-a]pyrazines

Article abstract of DOI:10.1007/s10593-007-0162-2

A study was carried out on the reaction of pyrrolo[1,2-a]pyrazines containing an alkyl, aryl, or aralkyl substituent at C-1 with trifluoroacetic anhydride. Trifluoroacetylation products may be formed either by reaction in the pyrrole ring or at the aryl o

Full text of DOI:10.1007/s10593-007-0162-2

Chemistry of Heterocyclic Compounds, Vol. 43, No. 8, 2007
TRIFLUOROACETYLATION
OF PYRROLO[1,2-a]PYRAZINES
V. I. Terenin, E. V. Kabanova, N. A. Tselishcheva, A. S. Ivanov, and N. V. Zyk
A study was carried out on the reaction of pyrrolo[1,2-a]pyrazines containing an alkyl, aryl, or aralkyl
substituent at C-1 with trifluoroacetic anhydride. Trifluoroacetylation products may be formed either by
reaction in the pyrrole ring or at the aryl or aralkyl groups at C-1. Products of electrophilic substitution
at C-6 are formed in the trifluoroacetylation of pyrrolo[1,2-a]pyrazines containing at C-1 a substituent
bulkier than a methyl group but lacking substituents at C-6 (the α-position of the pyrrole ring).
Keywords: pyrrolo[1,2-a]pyrazine, trifluoroacetic anhydride, trifluoroacetylation.
The pyrrolo[1,2-a]pyrazine bicyclic aromatic system has not been studied extensively, perhaps due to
the difficulties in its preparation and its relatively low reactivity. The relative stability of the
pyrrolo[1,2-a]pyrazine system to the action of weak electrophilic agents is indicated, for example, by the
formation of the 6-acetyl derivative in only 16% yield upon heating 1,7-dimethylpyrrolo[1,2-a]pyrazine with
excess acetic anhydride at reflux for 24 h [1]. The bromination of unsubstituted pyrrolo[1,2-a]pyrazine leads to a
1:1 mixture of 8-bromo and 6,8-dibromo derivatives [2, 3], while formylation of this model leads to
8-formylpyrrolo[1,2-a]pyrazine in 60% yield as the authors [2] affirm, although the 1H NMR spectrum given for
this compound leaves doubt concerning its structural identification. Paudler and Dunham [3] were unable to
formylate unsubstituted pyrrolo[1,2-a]pyrazine by the Vilsmeier-Haack procedure. Attempts to obtain nitroso or
azo derivatives of pyrrolo[1,2-a]pyrazines in reactions with nitrous acid and phenyldiazonium chloride also
proved unsuccessful [4].
Hence, we undertook a systematic study of the behavior of pyrrolo[1,2-a]pyrazines 1-10 in reactions
with electrophiles such as acylation with trifluoroacetic anhydride, which is a stronger acylating agent than
acetic anhydride. The trifluoroacetyl cation is a rather strong electrophile. Thus, the acylation of pyrroles by
trifluoroacetic anhydride proceeds rapidly at 0°C [5]. In previous work [6], we showed that
dipyrrolo[1,2-a:2',1'-c]pyrazines form ditrifluoroacetyl derivatives as the major reaction products with excess
trifluoroacetic anhydride even at room temperature. On the other hand, much more complicated behavior is
found for 3,4-dihydropyrrolo[1,2-a]pyrazines, for which the direction of the reaction depends on the structure of
the starting compounds and substrate/reagent ratio [7].
The α-position of the pyrrole ring in 1-methylpyrrolo[1,2-a]pyrazine (1) is unoccupied and we might
expect that the most likely product in its reaction with trifluoroacetic anhydride would be
6-trifluoroacetylpyrrolo[1,2-a]pyrazine by analogy to acylation by acetic anhydride [1]. However, the reaction of
1 with a 2.5-fold excess of trifluoroacetic anhydride in benzene (method A) yielded three products. NMR
spectroscopy and mass spectrometry indicated the formation of 1-(3,3,3-trifluoro-2-oxopropylidene)-
__________________________________________________________________________________________
M. V. Lomonosov Moscow State University, Chemistry Faculty, Moscow 119899; Russia; e-mail:
vter@org.chem.msu.ru. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1226-1233,
August, 2007. Original article submitted March 16, 2007.
1038
0009-3122/07/4308-1038©2007 Springer Science+Business Media, Inc.

1,2-dihydropyrrolo[1,2-a]pyrazine (11), 1-(3,3,3-fluoro-2-oxopropylidene)-6-(trifluoroacetyl)-1,2-dihydropyrrolo-
[1,2-a]pyrazine (12), and 1-(3,3,3-trifluoro-2-oxopropylidene)-8-(trifluoroacetyl)-1,2-dihydropyrrolo[1,2-a]-
pyrazine (13).
7
8
6
1 Me
N
N
4
COCF3
3
1
N
COCF3
COCF3
+
COCF3
N
+
F3COC
N
NH
NH
NH
11
12
13
Similar trifluoroacetylation results leading to trifluoroacetonyl derivatives were obtained previously for
methyl-substituted azines such as pyridine or pyrimidine [8]. Pyridine was shown to promote this reaction.
The yield of product 11 is enhanced while the yields of 12 and 13 were reduced to trace amounts when
the acylation of 1 was carried out with a 2.5-fold excess of trifluoroacetic anhydride in the presence of pyridine
(method B). Increasing the amount of reagent to a 10-fold excess and the acylation reaction time to 72 h
(methods C and D) led to the exclusive formation of ditrifluoroacetyl derivatives 12 and 13 (Tables 1-3).
TABLE 1. Characteristics ot Compounds Synthesized
Found, %
——————
Calculated, %
Com-
pound
Empirical
formula
Yield, %
(method)
mp,°С
С
H
N
11
12
С10H7F3N2O
52.22
52.64
44.52
44.46
2.84
3.09
1.65
1.87
12.06
12.28
8.84
8.64
145-146
32 (A), 44 (B)
C12H6F6N2O2
240-250
(dec.)
11 (A), 2 (B),
31 (C), 78 (D)
13
C12H6F6N2O2
44.15
44.46
1.94
1.87
8.35
8.64
230-240
(dec.)
12 (A), 3 (B),
34 (C), 14 (D)
14
15
16
17
18
19
20
21
C11H9F3N2O
C12H11F3N2O
C12H11F3N2O
C15H9F3N2O
C13H7F3N2OS
C14H13F3N2O
C16H11F3N2O
C18H10F6N2O2
53.97
54.55
55.69
56.25
55.89
56.25
61.87
62.07
52.58
52.70
59.65
59.57
63.57
63.16
52.54
54.01
3.67
3.75
4.18
4.33
4.27
4.33
3.25
3.13
2.45
2.38
4.50
4.64
3.46
3.64
2.58
2.52
11.89
11.57
11.12
10.93
10.54
10.93
9.59
9.65
9.38
9.46
9.85
9.92
9.26
9.21
6.72
7.00
82-84
108-110
88-90
37 (A), 60 (B)
51 (A), 59 (B)
87 (A), 98 (B)
94 (A), 64 (B)
50 (A), 70 (B)
63 (B)
112-114
116-117
40-42
86-88
69 (B)
176-180
(dec.)
9 (B)
22
23
C11H9F3N2O
C13H8F6N2O2
54.19
54.55
47.25
46.17
3.63
3.75
3.10
2.38
11.62
11.57
7.06
8.28
214-215
4 (A), 46 (B)
212-214
(dec.)
6 (A), traces (B),
67 (C), 66 (D)
24
25
C11H11F3N2O2
C12H11F3N2O
49.25
50.77
55.89
56.25
4.09
4.64
4.44
4.33
10.55
10.77
10.74
10.93
144-146
126-128
64 (A)
5 (B)
1039

TABLE 2. Mass Spectra of Compounds 11-25
Com-
pound
m/z (Irel, %)
11
228 [M]+ (79.55), 160 (10.79), 159 (100), 132 (7.95), 131 (59.66), 104 (27.84),
103 (9.09), 78 (14.77), 77 (18.18)
12
13
324 [M]+ (71.40), 255 (100), 227 (19.28), 158 (27.64), 130 (17.22)
324 [M]+ (86.07), 255 (100), 227 (77.27), 177 (53.98), 158 (48.57), 130 (19.99),
103 (19.95), 79 (19.62)
242 [M]+ (94.34), 241 (59.82), 173 (100), 145 (24.53), 144 (22.37), 117 (17.65),
91 (24.15), 86 (21.76), 69 (12.26), 64 (14.77), 63 (17.94)
14
15
256 [M]+ (33.14), 255 (16.51), 241 (42.69), 229 (18.91), 228 (100), 187 (15.87),
159 (29.26), 158 (19.92), 144 (17.48), 131 (28.17), 117 (10.49), 103 (10.93), 90 (12.03),
77 (19.19)
16
17
18
19
256 [M]+ (100), 241 (77.63), 228 (53.22), 214 (12.04), 187 (31.79), 158 (6.00),
144 (15.16), 89 (5.62)
290 [M]+ (74.50), 221 (100), 193 (32.15), 192 (29.28), 168 (36.44), 140 (20.29),
139 (20.27), 70 (21.36), 63 (25.93), 51 (18.52)
297 (14.06), 296 [M]+ (73.05), 227 (100), 199 (21.88), 159 (18.72), 155 (10.59),
114 (12.56), 69 (19.39), 64 (18.37), 57 (18.28), 44 (91.90)
282 [М]+ (26.30), 253 (25.49), 242 (19.75), 241 (100), 156 (31.45), 144 (25.48),
58 (22.77), 44 (24.34), 43 (51.08)
20
21
22
304 [M]+ (43.48), 303 (100), 235 (13.66), 207 (25.13), 206 (35.25), 205 (21.45)
400 [M]+ (83.19), 331 (100), 303 (43.69), 206 (60.60), 205 (78.90), 117 (21.88)
242 [M]+ (72.17), 173 (100), 145 (64.88), 118 (31.86), 91 (12.57), 77 (14.14), 73 (16.52),
72 (20.40), 63 (18.19), 51 (18.07)
23
338 [M]+ (46.69), 269 (100), 241 (75.72), 191 (39.20), 172 (54.41), 171 (26.75),
86 (29.65), 69 (30.80), 63 (41.70)
24
25
147 (32.64), 146 (96.11), 145 (100), 104 (16.58), 69 (44.95), 51 (19.33), 45 (25.15)
256 [M]+ (27.88), 188 (15.20), 187 (100), 159 (15.49), 93 (20.22), 78 (25.17), 63 (30.01)
The trifluoroacetylation of pyrrolo[1,2-a]pyrazines with the pyrrole ring free in the α-position when the
substrate has a substituent at C(1) other than a methyl group proceeds selectively at the α-position of the pyrrole
ring. Thus, compounds 2-7 give 1-ethyl-, 1-propyl-, 1-(2-propyl)-, 1-phenyl-, 1-(2-thienyl)-, and 1-cyclopentyl-
6-(trifluoroacetyl)pyrrolo[1,2-a]pyrazines 14-19. Carrying out this reaction in the presence of pyridine leads to
enhanced yields of the reaction products (Table 1).
R
R
F3COC
N
N
N
N
2–7
14–19
2, 14 R = Et, 3, 15 R = Pr, 4, 16 R = i-Pr, 5, 17 R = Ph, 6, 18 R = 2-Th, 7, 19 R = c-C5H11
We should note that acylation of 1-benzylpyrrolo[1,2-a]pyrazine (8) with trifluoroacetic anhydride is
more ambiguous and leads to the formation both of the predominant 6-trifluoroacetyl derivative,
1-(phenylmethyl)-6-(trifluoroacetyl)pyrrolo[1,2-a]pyrazine (20) in 69% yield and the ditrifluoroacetyl
derivative, (3,3,3-trifluoro-2-oxo-1-phenylpropylidene)-6-(trifluoroacetyl)-1-pyrrolo[1,2-a]pyrazine (21), in
9% yield.
A similar dependence for the result of trifluoroacetylation on the structure of the substituent at C(1) of the
pyrrolo[1,2-a]pyrazine system is found for these compounds substituted in the α-position of the pyrrole ring.
1040

COCF3
Ph
N
Ph
F3COC
N
Ph
F3COC
N
+
N
N
NH
21
20
8
Thus, the reaction of 1,6-dimethylpyrrolo[1,2-a]pyrazine (9) with trifluoroacetic anhydride by
method A gave two products analogous to 12 and 13 in low yields: 1-(3,3,3-trifluoro-2-oxopropylidene)-
6-methyl-1,2-dihydropyrrolo[1,2-a]pyrazine (22) in 4% yield and 1-(3,3,3-trifluoro-2-oxopropylidene)-
6-methyl-8-(trifluoroacetyl)-1,2-dihydropyrrolo[1,2-a]pyrazine (23) in 6% yield.
COCF3
Me
Me
N
Me
N
COCF3
+
Me
N
COCF3
N
NH
NH
9
22
23
In addition to 22 and 23, 1,6-dimethylpyrrolo[1,2-a]pyrazinium trifluoroacetate (24) was isolated from
the reaction mixture. Trifluoroacetate 24 is probably the result of the reaction of starting pyrrolopyrazine 9 and
trifluoroacetic acid formed during the reaction. The formation of an analogous by-product,
2-methyl-3H-indolizinium trifluoroacetate, has been observed in the trifluoroacetylation of 2-methylindolizine
[9]. The formation of 24 is not observed when the reaction is carried out in the presence of pyridine, which binds
the acid.
The acylation of pyrrolo[1,2-a]pyrazine 9 by trifluoroacetic anhydride in the presence of pyridine
(method B) leads predominantly to the formation of monotrifluoroacetyl derivative 22 in 46% yield, while
significantly increasing the excess of anhydride and the reaction time (methods C and D) leads to the formation
of 23 in good yields (66-67%).
A mixture of acylation products is formed in the reaction of 1-ethyl-6-methylpyrrolo[1,2-a]pyrazine (10)
with trifluoroacetic anhydride. Only one compound could be isolated with low yield from this reaction mixture.
1H NMR spectroscopy and mass spectrometry indicated that this product was 1-ethyl-6-methyl-8-(trifluoro-
acetyl)pyrrolo[1,2-a]pyrazine (25).
COCF3
Et
Et
Me
N
Me
N
N
N
25
10
TABLE 3. 1H NMR Spectra of Compounds Sinthesized
Com-
pound
Solvent
2
Chemical shifts, δ, ppm (J, Hz)
1
3
11
12
CDCl3
5.99 (1Н, s, CHCOCF3); 6.80 (1Н, d, J3,4 = 5.4, Н-3);
6.82 (1Н, dd, J7,6 = 2.6, J7,8 = 4.3, Н-7); 7.10 (1Н, d, J8,7 = 4.3, H-8);
7.34 (1Н, d, J4,3 = 5.4, H-4); 7.38 (1H, dd, J6,7 = 2.6, J6,8 = 1.0, H-6)
6.04 (1Н, s, CHCOCF3); 6.86 (1Н, dd, J7,6 = 2.6, J7,8 = 4.2, Н-7);
7.24 (1Н, d, J3,4 = 5.6, Н-3); 7.33 (1Н, d, J8,7 = 4.2, H-8);
7.74 (1H, dd, J6,7 = 2.6, J6,8 = 1.3, H-6); 7.84 (1Н, d, J4,3 =5.6, H-4)
Acetone-d6
Acetone-d6
6.31 (1Н, s, CHCOCF3); 7.57 (1Н, dd, J7,8 = 4.8, J8,4 = 0.55, Н-8);
7.64 (1Н, d, J3,4 = 5.6, Н-3); 7.77 (1Н, dq, J7,8 = 4.8, JH–F = 2.1, H-7);
8.83 (1Н, dd, J4,3 = 5.6, J4,8 = 0.6, H-4)
1041

TABLE 3. (continued)
1
2
3
13
Acetone-d6
7.51 (1Н, m, Н-7); 7.52 (1Н, s, CHCOCF3); 7.63 (1Н, d, J3,4 = 5.4, Н-3);
7.93 (1Н, d, J6,7 = 3.2, Н-6); 8.06 (1Н, d, J4,3 = 5.4, H-4)
DMSO-d6
CDCl3
7.35 (1Н, s, CHCOCF3); 7.46 (1Н, m, Н-7);
7.56 (1Н, d, J3,4 = = 5.4, Н-3);
7.95 (1Н, d, J6,7 = 3.3, H-6); 8.03 (1Н, d, J4,3 = 5.4, H-4)
14
1.44 (3Н, t, J = 7.5, СН2СН3); 3.14 (2Н, q, J = 7.5, СН2СН3);
6.91 (1Н, d, J8,7 = 5.2, Н-8); 7.70 (1Н, m, Н-7);
8.05 (1Н, d, J3,4 = 5.0, Н-3); 9.40 (1Н, d, J4,3 = 5.0, Н-4)
Acetone-d6
Acetone-d6
1.40 (3Н, t, J = 7.4, СН2СН3); 3.16 (2Н, q, J = 7.5, СН2СН3);
7.16 (1Н, d, J8,7 = 5.0, Н-8); 7.78 (1Н, m, Н-7);
8.12 (1Н, d, J3,4 = 4.7, Н-3); 9.36 (1Н, d, J4,3 = 4.7, Н-4)
15
16
1.01 (3Н, t, J = 7.5, СН3); 1.88 (2Н, m, СН2СН2СН3);
3.08 (2Н, t, J = 7.5, СН2СН2СН3); 7.16 (1Н, dd, J8,7 = 5.0, J8,4 = 0.8, Н-8);
7.77 (1Н, dq, J7,8 = 5.0, JН–F = 2.10, Н-7); 8.09 (1Н, d, J3,4 = 4.7, Н-3);
9.34 (1Н, d, J4,3 = 4.7, Н-4)
1.43 (6Н, d, J = 6.8, СН(СН3)2); 3.55 (1Н, m, J = 6.8, СН(СН3)2);
6.96 (1Н, dd, J8,7 = 5.0, J8,4 = 0.8, Н-8);
CDCl3
7.71 (1Н, dq, J7,8 = 5.0, JН–F = 1.9, Н-7); 8.03 (1Н, d, J3,4 = 4.8, Н-3);
9.42 (1Н, d, J4,3 = 4.8, Н-4)
17*
18
CDCl3
7.08 (1Н, dd, J8,7 = 5.0, J8,4 = 0.8, Н-8); 7.55-7.58 (3Н, m, H-р,m Ph);
7.74 (1Н, dq, J7,8 = 5.0, JН–F = 2.0, Н-7); 7.92 (2Н, m, H-о Ph);
8.21 (1Н, d, J3,4 = 4.7, Н-3); 9.53 (1Н, dd, J4,3 = 4.7, J4,8 = 0.8, Н-4)
Acetone-d6
7.30 (1Н, dd, Jα,β = 5.1, Jβ,β' = 3.9, Н-β Th);
7.54 (1Н, dd, J8,7 = 5.0, J8,4 = 0.9, Н-8);
7.81 (1Н, dd, Jα,β = 5.0, Jα,β' = 1.0, Н-α Th);
7.91 (1Н, dq, J7,8 = 5.0, JН–F = 2.0, Н-7);
8.09 (1Н, dd, Jβ,β' = 3.9, Jα,β' = 1.0, Н-β' Th);
8.20 (1Н, d, J3,4 = 4.7, Н-3); 9.49 (1Н, dd, J4,3 = 4.7, J4,8 = 0.9, Н-4)
19
20
21
22
CDCl3
1.74–2.19 (8Н, m, –(СН2)4); 3.67 (1Н, q, J = 8.4, –СН cyclopentyl);
6.96 (1Н, d, J8,7 = 5.1, Н-8); 7.70 (1Н, m, Н-7);
8.06 (1Н, d, J3,4 = 4.7, Н-3); 9.40 (1Н, d, J4,3 = 4.7, Н-4)
CDCl3
4.44 (2H, s, –CH2Ph); 6.86 (1Н, dd, J8,7 = 4.8, J8,4 = 0.5, Н-8);
7.23–7.36 (5Н, m, Ph); 7.65 (1Н, dq, J7,8 = 4.8, JН–F = 1.9, Н-7);
8.07 (1Н, d, J3,4 = 4.7, Н-3); 9.43 (1Н, dd, J4,3 = 4.7, Н-4)
CDCl3
5.01 (1Н, d, J8,7 = 5.2, Н-8); 7.22 (1Н, d, J3,4 = 5.7, Н-3);
7.27 (1Н, dq, J7,8 = 5.2, JН–F = 2.0, Н-7); 7.35-7.53 (5Н, m, C6H5);
9.00 (1Н, dd, J4,3 = 5.7, Н-4)
CDCl3
2.49 (3Н, s, 6-СН3); 5.95 (1Н, s, CHCOCF3);
6.61 (1Н, d, J7,8 = 4.3, Н-7); 6.85 (1Н, d, J3,4 = 5.5, Н-3);
7.05 (1Н, d, J8,7 = 4.3, Н-8); 7.20 (1Н, d, J4,3 = 5.5, H-4)
Acetone-d6
2.54 (3Н, s, 6-СН3); 5.98 (1Н, s, CHCOCF3);
6.69 (1Н, dd, J8,7 = 4.3, J8,4 = 0.5, Н-7); 7.26 (1Н, d, J3,4 = 5.8, Н-3);
7.28 (1Н, d, J7,8 = 4.3, Н-8); 7.62 (1Н, d, J4,3 = 5.8, H-4)
23
24
Acetone-d6
Acetone-d6
2.61 (3Н, d, J = 0.8, 6-СН3); 7.32 (1Н, m, Н-7); 7.44 (1Н, s, CHCOCF3);
7.64 (1Н, d, J3,4 = 5.5, Н-3); 7.80 (1Н, d, J4,3 = 5.5, Н-4)
2.70 (3Н, s, 6-СН3); 2.93 (3Н, s, 1-СН3); 7.15 (1Н, d, J7,8 = 4.3, Н-7);
7.64 (1Н, d, J8,7 = 4.3, Н-8); 7.68 (1Н, d, J4,3 = 5.5, Н-4);
8.26 (1Н, d, J3,4 = 5.5, Н-3)
25
CDCl3
1.30 (3Н, t, J = 7.4, СН2СН3); 2.52 (3Н, s, 6-СН3);
3.46 (2Н, q, J = 7.4, СН2СН3); 7.22 (1Н, m, Н-7);
7.68 (1Н, d, J3,4 = 4.4, Н-3); 8.00 (1Н, d, J4,3 = 4.4, Н-4)
_______
*
13С NMR spectrum (CDCl3), δ, ppm: 107.56, 119.06, 132.84 (С-3,4,8);
116.90 (q, J = 289, CF3); 125.28 (q, J = 3.9, C-7); 128.65, 128.86
(o,m-C6H5); 130.33 (p-C6H5); 136.91 (C-9); 154.06 (C-1); 170.14 (q,
J = 35.8, C=O).
1042

Thus, the trifluoroacetylation of pyrrolo[1,2-a]pyrazines with various substituents at C(1) is a ambiguous
reaction. The structure of the reaction products is a function of the substituents. The formation of substitution
products at the alkyl or aralkyl group is possible in the case of alkyl or aralkyl substituents at C(1).
EXPERIMENTAL
1
The H and 13C NMR spectra of all the products were taken on a Varian VXR-400 spectrometer at
400 MHz with TMS as the internal standard. The mass spectra were taken on a Kratos mass spectrometer with
70 eV ionization energy. The reaction course was monitored by thin-layer chromatography on Silufol UV-254
plates. Starting pyrrolo[1,2-a]pyrazines 1-10 were prepared according to our previous procedure [10].
Trifluoroacetylation of Pyrrolo[1,2-a]pyrazines (General Method). A. A solution of
pyrrolo[1,2-a]pyrazine (3 mmol) in dry ether (10 ml) was cooled with ice and then a solution of trifluoroacetic
anhydride (7.5 mmol) in ether (10 ml) was added dropwise with stirring. The reaction mixture was stirred for
5-7 h at room temperature, then poured into cold water, and extracted with chloroform. The extract was dried
over 3 Å sieves and evaporated in vacuum. The residue was subjected to chromatography on a column packed
with silica gel (100/160). The eluent was benzene or 1:3 ethyl acetate-petroleum ether. The products were
recrystallized from heptane.
B. A mixture of pyrrolo[1,2-a]pyrazine (3 mmol) and pyridine (7.5 mmol) in dry ether (10 ml) was
cooled with ice and a solution of trifluoroacetic anhydride (7.5 mmol) in ether (10 ml) was added dropwise
with stirring. The reaction mixture was stirred for 5-7 h and then treated as in method A.
C. A solution of trifluoroacetic anhydride (30 mmol) in ether (15 ml) was added dropwise with stirring
to pyrrolo[1,2-a]pyrazine (3 mmol) in dry ether (10 ml) with ice cooling. The reaction mixture was stirred at
room temperature for 72 h and then treated as in method A.
D. A solution of trifluoroacetic anhydride (30 mmol) in ether (15 ml) was added dropwise to an
ice-cooled mixture of pyrrolo[1,2-a]pyrazine (3 mmol) and pyridine (30 mmol) in dry ether (15 ml). The
reaction mixture was stirred at room temperature for 72 h and then treated as in method A.
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